Читать книгу How to Build a Human: Adventures in How We Are Made and Who We Are - Philip Ball - Страница 9

So far, nothing beats sex. Biologically, I mean. If you want to grow a human, you need a sperm and an egg cell – the two cell types called gametes. And you need to get them together. That’s an objective towards which an immense amount of our culture is geared.

In describing the process in which a fertilized egg develops into a person, I hope in this chapter to give back some of the strangeness, the proper unfamiliarity, to embryology: to show how removed our individual origins are from the comforting intimacy of the gracefully curled fetus that is generally our first ultrasonic glimpse of a new human person.

We are folded and fashioned from flesh in its most basic form, according to a set of instructions that is far removed from a kind of genetic step-by-step. We are shaped from living clay according to rules imperfectly known and often imperfectly executed, and which orchestrate a dance between the cell and its environment.

But there are many things you can potentially fashion from clay, if you know how to work the wheel. As we come to understand more about the emergence of the human ex ovo, we perceive new possibilities, new beginnings and routes and directions. And we change from watchers to makers.

* * *

There is no new narrative of human-growing that does not need to reckon with the preconceptions (so to speak) created by sex. Mary Shelley could not, in her day, make that context explicit – but Victor Frankenstein’s terror of his wedding night tells us all about the psychosexual undercurrents in his onanistic act of creation. I won’t therefore attempt the same evasion as the school biology lesson by beginning the embryo’s tale with sperm meeting egg; by that stage sex has, as we’ll see, already imposed itself on the story.

We should in any case be continually amazed, surprised and possibly even a little proud at how imaginatively we have elaborated, ritualized and celebrated the urge to procreate. This shouldn’t be seen so much as proof that evolutionary psychology can “explain” culture – the banal observation that because of our instinct for sexual reproduction we write stories like Romeo and Juliet and create entertainments like Love Island – but rather the opposite. Evolutionary psychology by itself offers a rather threadbare and reductionist narrative for understanding the rich tapestry of culture. Sure, we can attribute to the sexual drive everything from a worship of lingams in Indian tradition to the Tudor enthusiasm for prominent red codpieces,¹ the hegemony and variety of internet porn and the exquisite faux-pheromone concoctions of perfumeries. But then we will have not really said much that illuminates the particulars of any of those diverting cultural phenomena, will we?

It’s tempting to suppose that the bare biology of reproduction is quite distinct from the human mechanics and its attendant rituals, its messiness and epiphanies and calamities. But we rarely make any statement about biology, and least of all about the biology of making humans, that is devoid of a culturally shaped narrative. If we imagine we can start talking about new ways to grow humans (and parts of humans) that do not inherit some aspects of the stories we tell about how we do it already, we are fooling ourselves.

The old ideas of generative male seed quickening the passive female “soil” are evidently invested with patriarchal stereotypes. Within Christian tradition, conception long struggled to find accommodation with religious thought, being simultaneously a miraculous gift of God (and thus a moral obligation) and the fruit of sin. Within this view, the only “pure” conception in the history of humankind was one that took place two thousand years ago without intercourse and without seed, to dwell on the gestation of which was to risk heresy. And medieval theology willingly lent authority to the idea that to expel male seed not directed towards procreative possibility was even worse than to couple in lust, for it was liable to be taken up by demonic succubi and bred into monsters.

These were tales not just about the social side of sex but about its biological and medical aspects too. Until the nineteenth century, the health hazards of masturbation were considered a plain medical fact, as was the idea that a fetus in the uterus could be damaged by a mother’s bad thoughts. Probably every age has imagined itself mature beyond this mixing of science with folk belief and sociopolitical ideology, but let’s not make the same mistake.

So how does the sperm fertilize the egg? Why, the plucky little fellow has to race along the vaginal passage,² out-swimming its (his, surely!) peers in a Darwinian competition for survival. There sits the egg, plump and alluring – and in he dives, kicking off the process of becoming one of us. As Life’s science editor Albert Rosenfeld wrote in 1969, people are made from “the sperm fresh-sprung from the father’s loins, the egg snug in its warm, secret place; the propelling force being conjugal love.” (I think you’ll find it is actually hydrogen ions crossing cell membranes.)

We see this story not just in children’s books about how babies are made, but (less obviously) in some biology textbooks too, where the active role of the sperm and the passivity of the egg cell is typically stressed. It’s wrong. There is now good reason to think, for example, that the sperm’s entry into the egg is actively mediated by the egg (although even this description still somewhat anthropomorphizes the participants, imputing aims and roles). The fastest sperm are not necessarily the victors, because sperm needs conditioning by the female reproductive tract to make it competent to fertilize an egg. There is increasing evidence that in many species the female can influence which sperm is involved in fertilization – for example by storing sperm from several mates under selective conditions, or ejecting it after sex. Some experiments on genetic outcomes of fertilization seem to imply the egg somehow selects sperm with a particular genotype, defying the conventional idea that once it gets to this stage the union of gametes is random.

It’s by means of narratives about sperm and egg getting together that we instruct our children about the “facts of life” – the definitive phrase seemingly designed to fend off the awkward questions they might otherwise ask. Questions like: Why this way? For doesn’t it seem an awfully messy, contingent and chancy way for genes to propagate, requiring a costly investment in wardrobe, grooming products and expensive meals? If children knew that parthenogenesis (development of the ovum without fertilization) was a reproductive option in the animal kingdom, I suspect many would think it dreadfully unfair that it is not available to humans. (Not only children, actually.)

So why these facts? Why go through the rigmarole of sex, if it doesn’t seem to be a biological sine qua non of reproduction?

No one really knows the answer. The usual one is that sexual reproduction, by combining the genes of two individuals, permits a beneficial reshuffling that can help stave off genetic disease. Organisms like bacteria that reproduce by simple cell division, generating clones, will gradually accumulate gene mutations from one generation to the next. As most mutations are detrimental or at best have no discernible effect on fitness, this can’t be a good thing. But bacteria proliferate exponentially and rapidly, and it doesn’t much matter if many genetically disadvantaged lineages die off, so long as there are a few that acquire mutations that improve fitness. In a rapidly growing bacterial colony, the mutations give the population a chance to explore a significant amount of “gene space” and find good adaptations. It’s for much the same reason that bacteria have evolved mechanisms to transfer genes directly from one to the other in a non-hereditary process called horizontal gene transfer.

Organisms that reproduce slowly and sparsely, like humans, don’t enjoy a bacterium’s capacity to “try out” many mutations. But sex is a way to spread them more rapidly, by allowing new combinations of gene variants to be created at a stroke from one generation to the next.

Clonal reproduction is also risky as it tends to put all a population’s eggs in one basket (to rather abuse a metaphor). Along comes some virus that exploits a bacterium’s vulnerabilities, or a change in conditions such as drought or extreme cold, and the whole colony could be wiped out – unless a few individuals are fortunate enough to possess gene variants that can withstand the threat. That’s also why genetic diversity is good for a population. And again, sexual recombination of genomes provides some of that.

So sex is a way for slowly reproducing organisms like us to eject “bad” genes and acquire “good” ones. It recommends that the organisms become dimorphic – that there be two distinct sexes, to ensure that an organism doesn’t end up combining its own sex cells, which would rather defeat the object. Or at any rate, there must be more than one sex: there’s no obvious reason why it should be limited to two, and indeed some fungi have thousands of different “sexes”.³

From this basic requirement for a distinction between types of sex cell (gametes) stems all the rest of the exciting and confusing features of sexual dimorphism. It helps if the two sexes are distinguishable at a glance, to save the wasted effort (since generally it does cost time and effort, sometimes considerably so) of trying to mate with another individual with which that is not possible. (It also makes complete sense that those impulses and signals will not be equally strong, or present at all, in all individuals, making homosexuality a natural and common phenomenon in animals.)

Once those differences exist, they are apt to get amplified, diversify, sometimes way out of proportion. If you’re going to have sex, it’s likely that your behavioural traits will evolve to let you spot the fittest partners and to advertise your own fitness. Each sex will evolve methods of assessing mates, and outward indicators of fitness will elicit attraction in the opposite sex. Some of these make physiological sense: a lot of muscle suggests dominant males with good survival skills, wide hips in females imply superior child-bearing capacity. Other sexual signals may end up being rather arbitrary – it’s not obvious why body hair on our male ancestors would of itself confer any survival advantage. (Perhaps this was an example of “useless” signalling of fitness, like the peacock’s tail?) Some displays are simply about standing out from the crowd, like exotic bird plumage. Other facets of sexual attractiveness may be subtle: it seems likely, for example, that symmetrical facial features indicate that one’s developmental processes, which commonly unfold independently in the mirror-image halves of the body, are robust against random variations, giving the individual better health prospects. For all the elaborateness of some mating rituals in other animals, they might – if they could – count themselves lucky that these sexual signals and responses don’t get refracted through culture as they do with humans to the point where it can all get overwhelmingly confusing.

Now, this is certainly one way to talk about the evolution and origin of sex, but it invokes an uncomfortable amount of teleology. Sex doesn’t really exist in order to create genetic diversity. Nothing happens in evolution in order to produce a particular end result. It makes intuitive sense for us to speak like this, but the fact is that sex evolved because those early organisms that became able to fuse their cells and chromosomes somehow produced more robust populations than those that lacked this ability. Sexual reproduction might be a more or less inevitable consequence of evolution by natural selection, once it gives rise to a particular kind of complex organism, much as snowflakes are an inevitable consquence of the laws of physics and chemistry playing out in a particular environment. Evolutionary biologists say that sex is a successful evolutionary strategy, although this again imputes a sort of foresight to evolution that it doesn’t possess.

While these arguments for the value of sex surely have a lot going for them, they can’t be the whole answer. Sex is not essential for all higher vertebrates. Parthenogenesis occurs in many different types of animal, including insects such as mites, bees and wasps, and some fish, reptiles and amphibians. In a few such cases, reproduction can happen either with sex or without. Sometimes that’s by design – for example, parthenogenesis is thought to be an option for mayflies as a defence against a lack of males. (The same useful trait arises in the women of the male-free society in Charlotte Perkins Gilman’s utopian feminist novel Herland (1915).) In other cases it occurs by accident, unfertilized eggs just happening rarely to develop into embryos. Komodo dragons are among the larger creatures that can reproduce this way.

The reasons and mechanisms for parthenogenesis are varied and sometimes rather complicated. But one thing you can say for sure is that, in organisms for which it can take place, evolution has not seen fit to rule it out. To put it another way, there is nothing obviously necessary about sex, and assessing the benefits of sexual reproduction over other methods of propagating is a subtle and perhaps context-dependent business.⁴ As far as evolution is concerned, it is just a matter of whatever works.

* * *

There’s a complication with sex. Each of our body cells has two sets of chromosomes, and therefore dual copies of each gene, one inherited from each parent. But if one of these cells in a female simply fused with one from a male, the resulting cell would have four sets of chromosomes. That’s too many, and the cell couldn’t function properly. So organisms that reproduce sexually have evolved special kinds of cells that possess only one copy of each chromosome. These are the gametes, and they are found only in the gonads: the ovaries and testes.

Gametes are made from a specialized type of cell called a germ cell. The germ cells have doubled chromosomes (they are said to be diploid) just like somatic cells, but in a special kind of cell division called meiosis they divide into gametes in which these chromosomes have been carefully segregated into two. Cells with just a single set of chromosomes are said to be haploid.

Normal cell division (mitosis) involves replication of the chromosomes accompanied by their separation so that each daughter cell receives the full complement. Meiosis is even more complicated, because the existing chromosomes have to be divided precisely in two and shipped off to their respective destinations.

Actually it’s worse than that. Meiosis happens in two stages, and the overall result is that a single, diploid germ cell replicates its chromosomes once and divides twice to end up with four haploid gametes. As in mitosis, the process by which the chromosomes are divided uses a spindle-like structure made from fibrous protein. The chromosomes become attached to the fibres and are drawn towards opposing poles of the spindle located in the two lobes of the dividing cell.

Crucially, the chromosomes undergo some shuffling in this process. The pre-meiosis germ cell, recall, has one of each of the 23 types of chromosome from the mother, and a second copy of each from the father. Which of the poles of the spindle each chromosome is drawn towards is random, and so the diploid cells made by division of the germ cell have a random combination of maternal and paternal genes.⁵ The haploid gametes that eventually emerge from the process then have a thoroughly scrambled single set of chromosomes: with 23 pairs of chromosomes in all, there are 2²³, or about 8 million, possibilities. These are combined with a similar range of options in the other gamete when egg and sperm unite, so you can see that having sex is a good way to produce genetic diversity.

Formation of the so-called primordial germ cells happens early in the development of a human embryo, around two weeks after fertilization. This is even before the gonads have started to form, which is to say, before the embryo has yet “woken up” to which sex it is. It’s as if the embryo is putting these cells aside while deferring the matter of whether they will be eggs or sperm. The gonads themselves will guide this process, sending out chemical signals that tell the primordial germ cells which sort of gamete to become. They’re ready to do that around week six of gestation, by which time the germ cells have migrated across the developing embryo to their destination. For yes, that development involves not merely cell division but also cell movement, a physical sorting in space to arrange the parts in the proper disposition.

Germ cells were first postulated by the German zoologist August Weismann in his 1892 book The Germ-Plasm: A Theory of Heredity. As that title suggests, this was a hypothesis as much about evolution as about embryology. The “plasm” here reflects the widespread notion, before Boveri and Sutton’s chromosomal theory of inheritance, that heredity was somehow transmitted via the “protoplasm” substance inside cells. As we saw earlier, Charles Darwin speculated that the particles responsible for inheritance, which he called gemmules, were collected from the body’s cells and transmitted via sperm and egg. Weismann was a staunch advocate of Darwinism, but he was convinced that there was a fundamental distinction between the somatic cells that made up the body’s tissues and the special cells called germ cells that gave rise to gametes. Any changes to the “plasm” of somatic cells could therefore play no part in heredity. To demonstrate that changes to the body of an organism are not inherited, Weismann cut off the tails of hundreds of mice and followed their offspring for five generations, each time removing the tails. Not once were any offspring born without tails.⁶ Any notion that “acquired characteristics” could be inherited, as in the pre-Darwinian theory of evolution proposed in the early nineteenth century by Jean-Baptiste Lamarck, could no longer be sustained.

In Weismann’s view, then, somatic cells are irrelevant to evolution. They are destined to die with the organism. But germ cells beget more germ cells – there is an unbroken line of germ cells (the germ line) down through the generations. It’s often said that the germ cells are thus immortal, although that’s an odd formulation – by that definition, we are all immortal simply by virtue of being able (if indeed we are) to produce offspring.

* * *

In the story of how to make a human “the natural way”, the fertilized egg is often portrayed as the end – at least, until the happy day that the baby emerges. All our traditional stories of people-making rely on that quantum leap from fertilization to birth. The dire moral warnings about pregnancy that loomed over adolescence (and in some cultures still do) make this the equation: bring together sperm and egg and you’ll get a baby! It’s a warning (sometimes needed, for sure) to experimenting teenagers, but becomes more like a promise in the narrative of IVF: to make that longed-for baby, all you need to do is unite the gametes. And if it doesn’t turn out that way, something has gone wrong. There is a single and inevitable road from fertilized egg to infant, and anything else is an aberration.

This is misleading. To put it starkly, most acts of non-protected penetrative sexual intercourse do not produce a baby – and when I say most, I mean 99.9 per cent. Even most fertilized eggs do not become babies – about 2 to 3 in 10 confirmed pregnancies abort spontaneously in miscarriage, but even those figures mask the 75 per cent or so of fertilized eggs that never get to the point of registering as a pregnancy at all, either because they don’t develop into a multi-celled embryo or because the embryo fails to implant in the uterus. That’s a puzzling thing about humans: we are unusually poor, within the animal kingdom, at reproducing. You have to wonder whether all the attention we give to sex is because we are so spectacularly bad at getting results from it.

Even to say “bad” is perhaps to collude with the moral imperative of the fertilized-egg-to-infant story; let’s just say that we are an anomaly, for reasons imperfectly understood. This calls into question the idea that sex really is “for” reproduction, as some religious moralists insist. If we were inclined to see procreation as a divine gift and imperative, one would at least need to grant that God expects us to have a heck of a lot of rehearsal.

The baby grows, of course, from a fetus: even children’s books tell us that. But in the common view the fetus is simply a baby – a person – that has not yet fully developed. Its proportions might be a little odd, its limbs blunter, but it is recognizably human. The classic images made in the mid-1960s by Swedish photographer Lennart Nilsson and presented in the book A Child Is Born (1965), have defined the view of our in utero existence ever since. They show the fetus floating freely in space, often lacking even an umbilical cord, like the iconic image from Stanley Kubrick’s 2001: A Space Odyssey three years later. Perhaps this “child” even sucks its thumb. But these images were actually made by artful arrangement of aborted fetuses – they were not in fact living organisms at all, much less in utero. They were curated to tell a reassuring story. (At least, so it might seem until you realize that it’s a story in which the mother has been edited out.)

By the time a fetus looks even vaguely human (which is what, loosely speaking, distinguishes it from an embryo), most of the important stuff has happened. Most of the dangerous hurdles have been cleared. And most importantly, the developing organism is already anthropomorphic, relieving us from any need to grapple with the strangeness of an entity evidently made of cells, which we might want to call human but would struggle to justify that intuition.

Yet it is the early embryo that reveals the true versatility, the genius, of our cells – and the unfamiliarity of the moment when those cells are not merely what we are made of, but what we are.

It might surprise you to discover – it surprised me – that when a woman first has a fertilized egg (a zygote) inside her body she is not technically pregnant. This is not some perverse biomedical fine print; it simply makes no sense to see things otherwise. A pregnancy test would show nothing, nor will it for the first four days or so after fertilization. The zygote divides by mitosis into two, then four, then eight cells and so on, and at this point these cells can form all the tissues needed in the embryo: they are called stem cells and are said to be totipotent.

In other words, every one of these cells could potentially become a separate embryo. In the early days of embryology, that was by no means clear. The German zoologist Wilhelm Roux thought, for example, that cells are headed towards different fates from the first division of the zygote. In 1888, he reported experiments on frog embryos at the two and four-cell stage, in which he destroyed one of the cells by lancing it with a hot needle. A single remaining cell from a two-cell embryo would then, he said, grow into a half-embryo, suggesting that it had even at that stage become assigned as the progenitor of that part of the body plan alone.

But Roux’s method was flawed, because he could not detach the remains of the ruptured cell from the intact one. This debris interfered with the subsequent growth of the embryo. In the 1920s and ’30s, German embryologist Hans Spemann performed a cleaner act of surgery on salamander embryos. By using a noose made from a single hair taken from a baby, he pinched early embryos in two and found that each of the resulting parts is able to grow into a complete embryo.⁷ In effect, Spemann made identical twins by artificial means. Because he produced two genetically identical embryos from a single initial one, you could also call this a process of cloning.⁸ Spemann and his co-workers used amphibian cells, because they are so large that the delicate manipulation could be done by hand – albeit an impressively steady one.

The ball of totipotent stem cells that is the human embryo floats freely in the fallopian tube (also called the oviduct), borne slowly towards the uterus. By day five, the embryo has become a ball of around 70 to 100 cells and has rearranged itself into a structure known as the blastocyst. By the time it arrives at the uterus, it has shed the protein coat called the zona pellucida that formed the protective shell of the original egg – it has “hatched” and is ready to implant.

The human embryo at around five days, called a blastocyst.

That ball of cells is not exactly the nucleus of a person. Most of the cells of the blastocyst became the mere housing and life support. Some of them form an outer layer enclosing a fluid-filled void: these are trophoblast cells, comprising the tissue called trophectoderm which will become the placenta. Others congregate into a clump on the inside, called the inner cell mass, which separates into the epiblast from which the fetus will grow, and the hypoblast that will eventually become the yolk sac. The epiplast consists of embryonic stem cells, capable of forming all the tissues of the body (but not the placenta): a capacity called pluripotency. Identical twins grow from two separate inner cell masses in a single blastocyst, whereas non-identical twins grow from two separate blastocysts, formed from distinct eggs fertilized by different sperms. Within a few days of implanting, the epiblast is covered in a layer of specialized cells called the primitive endoderm, derived from the hypoblast.

The human embryo at around day 10–11.

The fate of the embryo wholly depends on a successful implantation in the lining of the uterus. If this does not happen – which is the case around 50 per cent of the time – the embryo will be expelled in the menstrual cycle. Failure to implant is one of the common reasons why an IVF cycle does not work. No wonder, then, the division of labour in the blastocyst makes it seem that its priority is to those cells surrounding the epiblast, which won’t be a part of the fetus at all. For without implantation, it’s game over.

Implantation is a delicate and complex process involving a dialogue of hormones and proteins between the embryo and the cells of the uterine lining. In some ways it is more delicate and complex than fertilization itself. The placenta, for example, is made not just from the trophoblast layer of the blastocyst but also from tissues from the mother, called the decidua. The two types of cell, with different genetic makeup, have to work together to create a single, vital organ. Emotive and anthropomorphic metaphors suggest themselves, presenting implantation as an intimate collaboration between the tissues of mother and her “child”. But one might equally choose to speak of the blastocyst “invading” the uterine tissue: one “organism” colonizing another for its survival.⁹ Both are stories; neither is a neutral description of events (which story ever is?).

* * *

The best is about to come. Calling the part of the embryo fated to become the baby an “inner cell mass” is no euphemism: it really does seem to be a shapeless conglomerate. If we want to insist that baby-making is a miracle, what seems truly miraculous is not just that the inner cell mass makes a body but that, most often, it makes exactly the same type of body, with five fingers on each hand, with all facial features in the right place and fully functional, and with its battery of correctly positioned organs. It’s no surprise that development of the embryo occasionally goes awry; it is astonishing that it does so rather rarely.

When embryos start off as single cells, they have no plan to consult. Cells are programmed to grow and divide, but it isn’t meaningful to think of a human being as somehow fully inherent in a fertilized egg, any more than one can regard the complex convolutions of a towering termite mound as being programmed into each termite. The growth of an organism is a successive elaboration of interactions within and between cells: a kind of collaborative computation whose logic is obscure and convoluted, and the outcome of which is incompletely specified and subject to chance disturbances and digressions.

In this way, the job evolution has devised for those formative cells is an architectural one: a challenge of coordination in time and space. They have to move into position, to acquire the right fate at the right time, and to know when it is time to stop growing or to die.

Developmental biologists talk of this as “self-organization”. It could make the process sound quasi-magical, calling as it does upon the image of the cell as an autonomous being with aims and purposes. But many of the rules are now broadly understood.

Two key factors are at work. First, as the cells divide and multiply, they take on increasingly specialized roles, a process called differentiation. Thus, totipotent cells in a two or four-cell embryo become trophoblasts or the pluripotent stem cells of the epiblast. The latter go through further stages of differentiation that ultimately produce the specialized cell types found in muscle, skin, blood and so forth. We will see shortly how that happens.

Second, particular spatial arrangements may arise from cells actively moving through or across the growing organism or organ, or becoming sorted into clumps of different cell types by preferential stickiness, often between cells that are alike.

That cells have adhesive qualities joining them into aggregates was suggested in the 1890s by Wilhelm Roux. He was also able to disrupt frog embryos by vigorous shaking, which separated them into single cells. He found that those cells would join back together, which he attributed to some kind of attractive force.

Such “disaggregation” experiments were taken further in the early 1900s by marine biologist Henry V. Wilson, who found that sponges kept for a long time in an aquarium became “loose” and could be teased apart into individual cells. He achieved the same thing in fresh sponges by the simple measure of squeezing them through a piece of silk, which acted as a sieve that separated the cells. Again, those cells would reassemble if brought into contact to regenerate a living sponge. It was like a recapitulation of the evolution of primitive multi-celled organisms from colonies of single-celled ones (see the First Interlude, here). When Wilson did the experiment with different species of sponge, he found that cells from the same species would stick together selectively. Ernest Everett Just discerned in the 1930s that the reason for this selectivity had something to do with the cell membranes. The truth is that cells adhere via protein molecules protruding at their membrane surface (especially those belonging to the class called cadherins), which will bind to one another discerningly.

This notion of “tissue affinity” was developed around the same time by the German-American embryologist Johannes Holtfreter. In 1955, he and Philip Townes studied how the cells of amphibian tissues that had been disaggregated by exposing them to alkalis could reassemble from solution. Holtfreter largely outlined the concept of cell sorting that allows tissues of several cell types to adopt particular structures and arrangements.

The process of body formation (morphogenesis) is orchestrated by genes, and no wonder then that genes have been attributed such determinative power. Some researchers have made more apt comparisons to a musical score: genes tightly constrain but do not fully prescribe the performance. This is still a limited metaphor, because you can look at the score and figure out (if you’re a musician) pretty much how things will go. Not so with genes. Sometimes it is better simply to tell the story as it is, as simply as you can, rather than trying to pretend it is some other story.

Morphogenesis literally means shape-formation, but equally it is a question of cell specialization: the embryonic stem cells gradually lose their versatility as they divide, becoming geared instead to do the task of specific tissue types. Heart muscle cells must execute synchronized beating, pancreatic cells must secrete insulin, the nerve cells of the eye’s retina must respond to light, and so on. This happens not by cells gaining new properties, but rather by narrowing the possibilities inherently available to them by shutting down genes that aren’t needed. That’s what differentiation is all about.

The cells must know how and where to switch genes on and off as differentiation proceeds. How do they know? The cues come from the other cells and tissues around them.

Some of these signals are delivered as chemical messages, which, diffusing through the mass of cells, serve to define a kind of spatial grid that lets cells know where they are in the overall embryo and thus what their fate should be.

Imagine that a cell, or group of cells, at one place in the embryonic mass switches on a gene that produces some protein. And suppose that this protein can diffuse out of the cell, like water leaking out of a paper bag, and into other cells. Then the concentration of the protein throughout the embryo varies gradually from place to place, being greater nearest the cells that produce it and slowly diminishing with distance. If you could measure the protein concentration, you’d have some notion of where you are in the embryo relative to the source cells. You’d be able to sense your position. Think of it in the same way as finding your way to the kitchen of a large house by following the smell: the stronger it is, the closer you are.

These “position-marker” proteins are called morphogens, and cells are able to “sense” their concentrations. Morphogen concentration gradients allow regions of the embryo to become distinct from one another.

To see how this can work, let’s forget the human body for a moment and look at the development of a simpler embryo: that of the fruit fly. This humble creature became the paradigmatic representative of “complex life” in the early twentieth century, when its robustness and ease of breeding made it the ideal subject to study the mechanisms of genetic inheritance – an art of which Thomas Hunt Morgan was the master. There are, of course, substantial differences between humans and fruit flies, extending to their genetic and developmental fine print. In particular, fruit-fly embryos, unlike those of mammals, are not initially clusters of separate cells at all. Once fertilized, the ovoid fly egg starts to replicate chromosome-carrying cell nuclei, but just accumulates these around the edges of the egg. The nuclei only acquire their own cell membrane once the embryo has amassed 6,000 or so. This lack of cell membranes in the early embryo makes it particularly easy for morphogens to diffuse through it.

One simple way that gradients of diffusing molecular morphogens can mark boundaries is to think in terms of concentration contours. A contour denotes a threshold: a point where the concentration exceeds a certain value.

The fruit-fly embryo acquires its initial pattern features from morphogen threshold concentrations. Pretty much the first thing it does is to define which end will become the head and thorax, and which end the abdomen. In other words, the embryo acquires a front–rear axis. That is defined by a morphogen protein called bicoid. At the tip of the “head” (so-called anterior) end, the embryo produces bicoid, and this begins to diffuse down to the rear (posterior) end. The concentration falls smoothly from the anterior to the posterior end. Where it exceeds certain values, the bicoid protein will bind to the DNA within the embryo and activate other genes with vivid names like hunchback, sloppypaired 1 and giant (typically named because of the developmental defects that mutations in the genes can produce). How this switching occurs is complicated, not least because it also seems to depend on a gradient of another protein called caudal that diffuses from the opposite (posterior) end. But the outcome is that the embryo becomes quite sharply segmented into regions where different genes are expressed or not. Thus the uniformity of the embryo is destroyed: an anterior– posterior axis is established, along with the segments that will develop into the fly’s head, thorax and abdomen. It seems that similar gradients cause segmentation of the neural tube of vertebrates: the tissues that will become our brain and spinal column.

Gradients in the concentration of proteins bicoid and caudal from opposite ends of the fruit-fly embryo switch on genes at different positions that cause segmentation of the body plan.

Other diffusing morphogens produce other kinds of gradient, defining different axes of the emerging body. For example, a protein called dorsal is involved in setting up the top-to-bottom (dorsoventral) axis of the fruit-fly embryo that distinguishes the region that will become the back (where the larva will ultimately grow wings) from that which will become the belly. In each case, the gradient thresholds may turn particular genes on and off in a series of elaborations that begins with the crudest determinants of shape – the front/back and top/bottom axes, say – and works its way to the fine details.

The idea that chemical concentration gradients might control the development of embryos was first proposed at the start of the twentieth century by Theodor Boveri. By producing a chemical patterning signal that spreads into the rest of the embryo, one cell can determine the fate of other cells nearby. In 1924 Hans Spemann, together with Hilde Mangold, called such groups of cells “organizers”.¹⁰ Mangold transplanted groups of cells in amphibian embryos from one position to another and saw that they could induce the development of “out of place” features.

The British biologists Julian Huxley and Gavin de Beer verified the idea of organizers in the 1930s by manipulating the embryos of birds. They proposed that Spemann’s organizers create “developmental fields” of some kind that influence the course of development. Spemann had imagined this “field” as something like the magnetic or electrical fields of physics, but Huxley, de Beer and their contemporaries in this fledgling field of developmental biology suspected that the agent was a chemical one. The notion that these organizing centres define a sense of position within the emerging body plan through the action of morphogen concentration gradients was crystallized in the late 1960s by biologist Lewis Wolpert.

There’s a crucial part of this story that I’ve skipped over so far. The patterning of the fruit-fly embryo is kicked off by the production of the bicoid protein at the anterior tip of the egg. But what causes that production in the first place? How does the bicoid gene know it is at the anterior end?

The answer is that “mother tells it”. While the unfertilized egg is attached to the follicle of the mother fly, specialized cells called nurse cells deposit material needed to make bicoid – specifically, the RNA molecules that mediate the gene-to-protein conversion – into the anterior tip of the egg, so that developmental patterning is all ready to go when the egg is fertilized. Right from the outset, cells in the embryo are dependent on other cells around it to know what to do. It’s for similar reasons that a fertilized human egg can’t develop fully in isolation, if cultured in a test-tube. Implantation in the uterus wall is needed to give it a “sense of up and down”. Ectopic pregancies (within the fallopian tubes) show that such a signal doesn’t have to come from the uterus, however, and we’ll see later whether there might be other ways to do produce it in vitro.

This is why it is strictly incorrect to say – although it often is said – that all the information needed to grow a human being is in the genome of the fertilized egg, which is in turn supplied by the gametes that combined to make it. You could say that the human embryo also needs positional information supplied by its environment – specifically by the uterus lining. Furthermore, any particular cell in the developing embryo depends on receiving information from the surrounding cells in order to keep embryo growth on track. As the transplantation experiments of Huxley and de Beer showed, if you mess with that information then you screw up development, despite the fact that every cell retains its complete “genetic programme”.

Embryo development is thus not encoded from the outset in the genome, as if in some blueprint or instruction book. It relies on a precise expression of genetic information in time and space, which in turn depends on the proper coordination of many cells (including maternal ones) and is subject to chance events during the execution. To understand embryology and the growth of complex tissues and organisms, we shouldn’t imagine that we will find a set of instructions packed like a homunculus inside the zygote. Rather, we will need to discern and interpret the patterns of information flow (and the various sources of that information) as the process unfolds.

It’s rather as if the genome is a list of the words that feature in a book, but you need other information to put the words in the right order so that they become more than just assemblages of letters and may take on meanings. Those meanings are not inherent in the words themselves but may be determined by the words nearby, by allusions and interactions that leap from one part of the text to another – by context. Again, there is no perfect metaphor for illustrating how genes work in building an organism; doubtless this one would collapse too under pressure, so use it gently.

* * *

I won’t explain in detail how human embryogenesis differs from that of the fruit fly, but it’s worth understanding one of the most basic distinctions. For the human body doesn’t simply emerge imprinted on the inner cell mass of the blastocyst like stripes on an embryonic zebra.¹¹ Rather, the cells in the embryo move around, and the tissues grow, buckle and fold, to shape the body. It’s a highly active process, a kind of auto-origami happening in parallel with the appearance of distinctions between cell types. The first stage of this process, which for humans occurs around day 14 after fertilization (around the time that a pregnant woman might first notice a missing menstrual period), is called gastrulation. Some scientists regard this as the point where a mass of cells begins to produce an organism: as the beginning of personhood.

There is a lame joke that scientists still seem to find amusing about how, if a physicist were to study the cow, she would first simplify the question by approximating it as a sphere. It is rendered all the lamer by the fact that this is not so far from how nature approximates the human body – or the bovine one for that matter – in the first instance. For the most rudimentary idealization of our body might run thus: an inner tube for digestion from mouth to gut to anus, an outer layer of skin to create a boundary, and everything else packed into the space in between. At one end we’ll put the head – the anterior – and at the other end is of course the posterior. Gastrulation creates a structure very much like this (the word actually means “gut formation”). In some creatures, such as species of worms and molluscs, it really is that simple: gastrulation folds the embryo into a sort of fat tube or doughnut shape in which an inner tube connects mouth to anus, and the job is nearly done at a stroke.

For humans, it is rather more complicated. The embryo develops a central groove called the primitive streak, which will become the axis of the backbone and central nervous system: the beginning of the aforementioned neural tube. The subsequent folding is not easy to describe in words, but it creates the crescent-shaped structure that will become the fetus, connected to a yolk sac (involved in early embryonic blood supply) and attached to the placenta via the umbilical cord. The key point is that initially this gastrulated human embryo develops distinct types of tissue: its cells lose their pluripotency and start to specialize. The innermost layer, which will form the lining of the gut, is called the endoderm (“inner skin”). The outer layer, or ectoderm, generates the surface layer of the skin as well as the brain and nervous system. Between these layers is the mesoderm (“middle skin”), which is the primal fabric of the inner organs and tissues: the heart, kidneys, bone, muscles, ligaments and also the blood. At this stage, some of the embryonic stem cells are also set aside to become the germ cells: the precursors to the gametes (eggs and sperm).

Gastrulation of the human embryo and formation of the primitive streak.

And there you have it: the schematic human body, its cells launched on their road to specialization. The rest is refinement. For example, some neural cells in the head region develop (around week five of gestation) not into neurons but into the retinal cells of the eye. Some cells don’t differentiate where they first sit, but actively migrate through the embryo to where they need to be – we saw that the primordial germ cells do this. The sex organs develop identically at first in both sexes, becoming female organs unless triggered into the structures of the male if the cells have a Y chromosome instead of a second X. On the Y chromosome sits a gene denoted SRY, which controls other genes needed to develop male characteristics.

All of this refinement happens through cell dialogue. Molecular messages pass from cell to cell, each at the proper stage of development, so that cells get assigned their roles in collaboration with their neighbours. “The parts of each organ help the other parts to form,” explains cell biologist Scott Gilbert. It is because organoids like my mini-brain lack this information from surrounding tissues that their development – their morphology – is imperfect. To make a body or even a mature organ, cells need community.

* * *

The idea that genes involved in development interact and control one another via diffusing morphogens is only a part of the story of how embryos take on their form. The distinctions between cell types initiated by such signals become permanently imprinted on the cells as they develop into different tissues.

How can that be, if they still all share the same genome?

That problem was recognized by Thomas Hunt Morgan and others in the early days of molecular genetics, but no one really knew how to address it. So it was largely put to one side. The discovery of DNA’s genetic code in the 1950s and ’60s all but eclipsed the question, seeming as it did to promise an underlying simplicity in the way cells function. Already in 1941, Morgan’s former student George Beadle, along with biochemist Edward Tatum, had shown that genes (whatever they were – it wasn’t yet clear) encode protein enzymes. This became understood to mean that each gene has a unique corresponding protein. The key question was then how a gene made a protein. Crick and Watson’s double helix, zipped together with information-bearing nucleotide bases, seemed to deliver the answer: DNA carries the coded plan, and RNA and ribosomes are the machinery that does the translation.

But how do you get from a protein to the phenotypic effect of a gene on the unfolding organism? That wasn’t at all obvious. By the 1960s, the general idea was that genes act in some vague way to dictate the developmental programme, which was then envisaged merely as “an unfolding of pre-existing instructions encoded in the nucleotide sequences of DNA”, as American biologist-cum-historian-cum-philosopher Evelyn Fox Keller has put it. According to the French biochemist Jacques Monod, as far as gene action is concerned, “what’s true for [the bacterium] E. coli is true for the elephant.” What seemed to matter was establishing the common basis by which gene becomes protein. Somehow the rest – meaning the living organism itself – followed. Which would be all very well, if E. coli looked like an elephant.

In this picture, then, the answer to the question of development must reside in the gene sequence, and the ultimate goal of biology becomes the decoding of that sequence. This picture has been burnished for a remarkably long time, culminating in the Human Genome Project, which began in the 1990s and announced the almost complete sequencing of the human genome between 2001 and 2003.¹² The objective was simply to get the code, which took on the status of the “fundamental” information directing all biological activity. Meanwhile, genetics more broadly looked for correlations between genes and phenotypic outcomes. Exactly how and why genes exert their effects was a question long bundled up in the vague concept of “gene action” that, as Keller says, allowed scientists “to get on with their work despite almost complete ignorance of what that ‘action’ consisted of.” There was an implied hierarchy of causation in which genes were paramount, as reflected in Nobel laureate David Baltimore’s comment that the development of an organism involved the “greasy machines” of the cell directed by the “executive suite” of the genome. (Engineers are very familiar with this kind of prejudice.)

The resulting view was that development was a kind of painting by numbers of the plan in the genome. For a complex organism like us, that left an awful lot of instructions to be packed into the genes. As the Human Genome Project got underway, biologists estimated the number of genes the project would find as being somewhere between 140,000 and a lower limit, proposed by a few bold souls, of 26,000. Most put the figure at around fifty to seventy thousand.

The answer turned out to be 23,000.

This is often presented as a sobering example of how experts can get things wrong. It’s certainly that, but rarely does anyone identify the real moral: that the genome doesn’t work the way it was thought to.

Zoologist Fred Nijhout is one of the few to have come properly to terms with the implications. “A more balanced and useful view of the role of genes in development,” he says, “is that they act as suppliers of the material needs of development and … as context-dependent catalysts of cellular changes … they simply provide efficient ways of ensuring that the required materials are supplied at the right time and place.” They are less like Baltimore’s executive directors, and more like stewards guiding a crowd. It’s no coincidence that Nijhout sees things this way, because he is an expert on the genetics of butterfly wing patterns, where it is clear that just a few genes, creating interacting fields of influence through the diffusion and spreading of morphogens, can generate a startlingly diverse array of patterns and forms, dictated by the details of how the genes are expressed in time and space. It’s somewhat meaningless, in such a situation, to say what a gene does (beyond “encode a class of proteins”) without specifying where and when it acts.

The view now emerging is that a relatively small number of genes is able to generate the complexity of the human form, with its many different tissue types so precisely arranged and coordinated, because they act in networks that produce distinct patterns of gene expression varying over time. With 23,000 genes, the number of possible networks of influence is astronomical.

How do genes acquire and change their patterns of behaviour? The control, activation and silencing of genes in different cell types and at different stages of development is called epigenetics. The word literally implies something additional to genetics, but what it really connotes is that the observable outcome of genetic activity – the phenotype, such as the tissue type of a cell – isn’t determined by the genotype (that is, which genes are present), but by the question of which genes are active. Epigenetics is all about how genes become modified to alter whether, or how much, they are expressed.

There are several ways in which this can happen. One is by the attachment of molecular “tags” to the respective genes, which might act as markers that deter the machinery of transcription, suppressing gene expression. Some genes can be switched off, for example, by proteins that stick a so-called methyl group – a carbon atom with three hydrogen atoms attached – onto DNA bases in the gene, which forms a sort of “shield” that protects the gene against being transcribed and translated into a protein. Another molecular mechanism of epigenetic regulation involves chemical changes to the histone proteins around which a stretch of DNA is wrapped in the chromosomes.

Harder to understand than this attachment of “leave me alone” labels to genes, but equally important for epigenetics, are processes that involve the packaging of DNA in chromosomes. Remember that the combination of DNA and histone proteins in chromosomes goes by the name of chromatin. This stuff is rather systematically coiled up and stowed when the chromosomes are in the compact form (typically X-shaped) found in dividing cells. At other points in the cell cycle, chromatin can be unwoven and loosely strewn, in which case the transcription machinery can get to it more easily. So how “active” genes are can depend on how the corresponding regions of the chromosomes are packaged.

An example of this epigenetic gene regulation happens in female cells, which contain two copies of the X chromosome, one passed on from each parent. If both of them were active, they would produce more proteins from this chromosome than the cell needs, and that would cause problems. So one X chromosome is inactivated early in the development of the embryo. The choice of whether to silence the maternal or paternal X chromosome is made by each cell at random and then passed on to daughter cells when they divide. The result is that females end up with an equal blend of two types of cell throughout their body. This process of X-chromosome inactivation was first identified by geneticist Mary Lyon in the 1960s. It took many years to figure out how “X-silencing” occurs, but we now know that it involves a gene that switches on a series of events resulting in the packaging of the inactive chromosome into a tight bundle, inaccessible to transcription. All the genes are still there and are faithfully copied and passed on when cells divide, but the shape of the chromosome keeps them hidden.

Some epigenetic changes to DNA that regulate gene activity happen automatically as cells divide and mature: each cell type will have its own characteristic pattern of epigenetic modifications. This too is why development of a fertilized egg into an embryo and then a mature organism isn’t exactly just a matter of reading out a genetic programme. It involves a continual, ever-changing process of epigenetic editing of that programme, taking place through time and space.

* * *

In the mid-twentieth century, British embryologist Conrad Hal Waddington offered a metaphor for the process of epigenetic cell differentiation. He imagined cells in the early embryo traversing a landscape of possibilities: they begin their journey at a mountain peak and descend into valleys that branch like the channels of a river. At each branching point, the cell (more properly, the lineage of dividing cells) makes a decision about its subsequent fate: to become a progenitor of lung or heart, say. The consensus was that, once a lineage has descended into a valley, it can never reverse direction and go back uphill again.

The Waddington landscape. The balls represent the trajectories of different cell lineages, which begin in the single valley of totipotency as the zygote first begins to divide, and end in valleys representing different types of mature, differentiated cell.

Differentiation begins early. Indeed, it has happened even in the pluripotent embryonic stem cells of the epiblast, which have lost the totipotency of the earliest cells made from the dividing zygote. Already some of those first cells have been directed down the valley in Waddington’s landscape that leads to a placenta or a yolk sac, not to a part of the fetal body. The cells that make up the three layers of endoderm, mesoderm and ectoderm in the gastrulated embryo have undergone a further degree of differentiation, a further narrowing of choice.

It’s because of this specification of cell “fates” early in embryogenesis that the germ cells need to be formed so soon. Evidently a barely formed embryo doesn’t yet “need” eggs or sperm – but it must put aside the cells from which they will grow before they lose too much of their pluripotency. The germ cells, after all, have to make a totipotent zygote, so it won’t do if their chromosomes have already been heavily modified and silenced. Germ cells do have some epigenetic silencing of genes, although this too must be stripped away when the gametes combine to make a totipotent zygote.

This special dispensation for germ cells aside, epigenetic changes appear to be one-way. They partly account for how our body tissues remember and maintain their identity as they grow: why skin cells divide to produce more skin cells, and don’t spontaneously become muscle cells or stem cells. In other words, cell replication is somewhat more complex than merely a matter of copying the chromosomes. It’s necessary also to copy the epigenetic chromosomal modifications that give the cell its identity.

What this means is that each cell in our bodies, like each one of us, has a lineage: an ancestral history that starts with the zygote – and, except for a handful of germ cells (if we have children), ends in the grave. A liver cell has arisen from an embryonic stem cell via a succession of ancestors with intermediate characteristics, reflecting an ever greater specialization and loss of versatility. This notion of cell lineages was first articulated clearly by August Weismann when he drew up his fundamental distinction between somatic (“mortal”) and germ (“immortal”) cells.

When we tell the story this way, a new possibility becomes apparent. In cells during development, just as in organisms during evolution, genes can change. Every time a cell divides, there is a chance that some of the three billion base pairs in the genome will be miscopied – that the daughter cells will acquire mutations. Cells put a great deal of effort into avoiding such mistakes, employing a kind of molecular proofreading to check for errors in replication. All the same, the numbers are so vast that mutations are inevitable. It’s estimated that distributed within the chromosomes of our 37 trillion or so cells are about ten thousand trillion genomic mutations.¹³ Every one of our genes experiences somatic mutations at some point in our lives.

Most of these mutations, fortunately, don’t matter – they don’t affect a gene’s ability to do its job(s). But some have consequences. Most notoriously, gene mutations can lead to the cell dysfunctions that cause cancer (see here). Even potentially harmful mutations, though, might not matter if they happen late in development and so appear only in a few cells. Somatic mutations that arise during early embryo growth, on the other hand, may be passed on to all subsequent cells in that lineage, making the developing body a patchwork or “mosaic” with slightly but perhaps significantly different genomes. There are many diseases related to “mosaicism”, of which cancer is just one class. Somatic mutations leading to mosaicism are particularly common in brain neurons, and they are thought to be responsible for a range of brain and cognitive disorders, including some types of autism. Even benign mutations can manifest themselves in outward appearance (that is, phenotypically): for example, causing striped skin pigmentation called Blaschko’s lines or the red skin blotches called port-wine stains.

One particularly unusual but very rare kind of mosaicism happens when a cell in a male embryo fails to pass on its Y chromosome to the daughter cells, which, inheriting only the X, then develop as “female cells” by default. This can lead to a mixture of male and female characteristics in the embryo. Rare it may be, but this condition serves to remind us of the cell’s autonomy. Even in a body “meant” (to judge from the zygote) to be male, there is no global command that cells obey, and the “feminized” cells will feel no obligation to conform to the nature of their “male” neighbours.

Genetic variations along a cell lineage are, therefore, random. Epigenetic modifications that give rise to different cell types and tissues, on the other hand, are generally systematic and preordained in the genes – not in the sense that they will happen come what may, but that they are destined to be a part of the developmental programme so long as it proceeds without mishap. Some epigenetic changes aren’t preordained at all, though. They may take place in response to the contingent environment of a cell or organism, including unpredictable events arising from randomness within the network of interacting genes themselves. This is one reason why identical twins, who have the same genomes, may look rather different later in life. They have different environmental nudges, and this affects the epigenetic programming of their genes. Some dietary chemicals such as curcumin (found in curry spices) and resveratrol (in grapes) seem to have epigenetic effects on the folding-up of chromatin in cancer cells, while deficiencies of folate (a chemical in pulses and grains) can alter epigenetic patterns of methyl attachment to DNA. (Whether this means that red wine and tikka masala protect against cancer is another matter.) Drugs and pollutants can also act, for better or worse, via their influences on the epigenetic (as well as genetic) programming of cells.

Given that Waddington proposed the idea of an “epigenotype” – which he called a “whole complex of developmental processes between the genotype and phenotype” – in 1942, it is a little odd that epigenetics has been portrayed in recent years as a field that is “revolutionizing” biology. Perhaps that’s just how it looks if you’re starting from a simplistic view in which cells are nothing more than player-pianos orchestrated by their punched-hole genetic scripts – that’s to say, if you had a faulty story to begin with.

All the same, it is only in the past several decades that we have had a more detailed understanding of how epigenetics works at the scale of cells and molecules. There are still many holes in that understanding. Some researchers now talk in terms of an epigenetic code that imposes itself on and modulates the “all-powerful” genetic code. But epigenetics is a dynamic process, for which a “code” might be the wrong metaphor. Sure, there may be an epigenetic signature characteristic of, say, a fibroblast cell. But the epigenetic status of a human being is constantly changing and depends on our personal history.

It is the recognition of contingency in a cell’s epigenetic state that underpins the real revolution in biology. For, as the growth of my mini-brain from skin cells attests, the specification of cell fate is not irreversible. If we cling too strongly to the evolutionary metaphor of cell lineage, that sounds crazy: it’s like saying that you could be transformed back to a pre-human Australopithecus (more properly, to the common ancestor we Homo sapiens shared with that early hominid).

But for cells, such things are possible. The history of our flesh can be reversed and revised, and this completely transforms the possibilities for what it can become – and what we might do with it. We will see later how this can be achieved.

* * *

It should come as no surprise that there’s plenty of contingency and circumstance involved in the way genes, epigenetics and cell interactions combine to create a human being. Of course the environment can play a major and perhaps even catastrophic part. Drugs (licit and otherwise), alcohol, hormones and environmental contaminants entering the mother’s bloodstream during pregnancy can disrupt the process, for example, in ways that are transformative to the embryo or fetus.

We might tend to imagine that this is just a matter of a “plan for a person” that either proceeds as it should or gets thrown off course. But I will end this chapter by looking at one more way in which a simplistic picture of the person being a kind of “read-out” of the genes in a zygote can be profoundly misleading. The person – their body, their chromosomal inheritance of propensities – is not so easily condensed into a single type of cell. For just as human societies can be diverse, so can the cell societies that comprise a human individual.

Non-identical twins, for instance, may each have a mixture of red blood cells from both twins. Red blood cells are unique in the human body in having no chromosomes: they are produced not by cell division but by transformation of a special kind of cell in bone marrow. They fall into particular general classes – blood groups – depending on the chemical structure of protein molecules on the surface of the cells. Normally, each individual has red blood cells of a specific blood group, but twins can have a mixture of each twin’s blood group.

This was first discovered in non-identical twinned cattle calves by the American biologist Ray Owen in the 1940s. In 1953, British physicians Ivor Dunsford and Robert Race found a similar case of two distinct blood groups in a human, a patient denoted Mrs McK who was tested before donating blood. Mrs McK had no living twin, but she told the puzzled doctors that she had had a twin brother who had died at three months old. The mixture of blood types here come from the fact that twins share a blood circulation system in the uterus, and so may exchange blood-forming cells that continue to produce blood long after birth and perhaps for a lifetime.

This presence of cells from more than one “biological individual” persisting and carrying out their biological function in a single organism is said to make it a chimera. Robert Race coined the term in describing the case of Mrs McK, admitting that he was simply looking to give his paper a catchy title.

People can be chimeric in much more dramatic ways than this. Their entire bodies can be patchworks of cells that seem to come from two different people. One way this can arise is by the fusing, at a very early stage of development, of non-identical twin embryos in utero. In a demonstration of how our cells can adjust to “unforeseen circumstances”, these fusions can give rise to an anatomically normal individual whose cells got their genetic material from two different pairs of gametes: they are said to be tetragametic. This can happen even if the embryos that fused were of different sexes: the reproductive organs will then be decided by which set of cells in the merged embryo happens to produce them. But the chimeric person’s body as a whole is not specifically gendered one way or the other in terms of the usual XX/XY chromosomal distinction: it is a bit of both.

Chimerism can also arise from exchange of cells between an embryo and the mother carrying it. These two “individuals” are conjoined via the placenta, which, as I explained earlier, is a mixture of cells from both of them. But the placenta is a rather leaky barrier. So cells from the mother can become incorporated into the embryo and fetus, while the developing child’s cells may enter the body of the mother.

In fact, some degree of exchange, known as microchimerism, is normal. Many women who are pregnant with sons, for example, acquire some cells with Y chromosomes. What surprised researchers when this exchange came to light in the 1990s is that these fetal cells may persist and remain active, albeit at a low level, in the mother for many years after the child is born. But while microchimerism affects just a small proportion of the body’s cells, a process like embryo fusion to create a tetragametic chimera makes a person who is genetically heterodox through and through: some organs and body parts come from one embryo, some from another.

If I were a mixture of the flesh of “two people”, what would that make me? It is tempting to say that such an individual is indeed a mixture of two people in one. But that seems a profoundly odd and unhelpful way to look at the matter, for in what meaningful sense were those twin embryos “people” before they fused? These clusters of cells have only given rise to a single individual. This is just one of the ways in which quirks of developmental and reproductive biology undermine a simplistic determination to invest an embryo with unique personhood. A “person” is a higher-order concept, not to be reduced to genes or cells.

Still, our habits of thought and even our laws are challenged by these discoveries. DNA analysis of a tissue sample from a tetragametic woman may fail to confirm that her biological children are “hers”, if the sample does not happen to share chromosomes with her gametes. Such cases have come to light through genetic testing to confirm maternity in applications for social welfare benefits in the United States, leading to harrowing accusations of false claims of parentage. Some of these cases have highlighted how strongly we invest notions of personhood and identity in the character of our flesh and genes. In his book She Has Her Mother’s Laugh, science writer Carl Zimmer describes two such cases, saying that the discovery of their chimerism left these women with “haunting questions not only about their families but about themselves”. One woman wondered if she was only partly the mother of her children, despite having given birth to them, and partly their aunt. “I felt that part of me hadn’t passed on to them,” said the other woman. As Zimmer explains:

We use words like sister and aunt as if they describe rigid laws of biology. But despite our genetic essentialism, these laws are really only rules of thumb. Under the right conditions, they can be readily broken.

Yet I wonder. Not all cultures do use these words this way. It is common in Chinese society, for example, to call a close female friend of the family “aunt” even without any blood relation, and in the West “sisterhood” and “brotherhood” are widely used to express sympathetic bonds irrespective of sibling connections. Many cultures have a flexibility of familial relations that does not inevitably reduce them to blood and birth.

No, the problem here is not that biology destroys our traditional categories and concepts of human life, but that we too often now fall into the trap of imagining that biology can and should arbitrate on socially mediated questions of self and identity, family and kinship, sex and gender. Biology has a habit of declining that role, handing back (so I like to see it) the responsibility and saying, “you, not I, are the ones who care about these issues, so you must decide them for yourself.”