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CHAPTER 2
BODY BUILDING
GROWING HUMANS THE OLD-FASHIONED WAY
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.
