How to Grow a Human

Might we, then, call a genome not a blueprint but a recipe? The metaphor has rather more appeal, not least because many recipes assume implicit knowledge (especially in older cookbooks). But a recipe is still a list of ingredients plus instructions to assemble them. Genomes do not come with users’ instructions, more’s the pity. Harold offers a different image, allusive and poetic and all the more appealing for that:

I prefer to think of the genome as akin to Hermann Hesse’s Magister Ludi [aka The Glass Bead Game]: master of an intricate game of cues and responses, in which he is fully enmeshed and absorbed; a game that is shaped as much by its own internal rules as by the will of that masterful player.

If there was better public communication of the complex, contingent and often opaque relationship of genotype to phenotype, there might be rather less anxiety about the idea that genes affect behaviour. Small variations in each individual’s genetic make-up can have an influence – sometimes a rather strong one – not just what you look like but what your behaviour and personality are like. This much is absolutely clear: there is not a single known aspect of human behaviour so far investigated that does not turn out to show some correlation with what gene variants we have. Even habits or experiences as apparently contingent and environmental as the amount we watch television9 or our chance of getting divorced are partly heritable, meaning that the differences between individuals can be partly traced to differences in their genes.

Far from alarming us, this shouldn’t surprise us. We have always been content to believe that, for example, some people seem blessed with talents that can’t obviously be explained by their environment and upbringing alone. By the same token, some seem hardwired to find particular tasks challenging, such as reading or spatial coordination.

Yet perhaps because we have a strong sense of personal agency, autonomy and free will, many people are disturbed by the idea that there are molecules in our cells that are pulling our strings. They needn’t worry. It is precisely because genetic propensities are filtered, interpreted and modified by the process of growing a human cell by cell that they don’t fully determine how our bodies turn out, let alone how our brains get wired … let alone how we actually behave.

Genes supply the raw material for developing our basic cognitive capabilities – to put it crudely, they are a key part of what allows most human embryos to grow into bodies that can see, hear, taste, that have minds and inclinations. But how they exert their effects is very, very complicated. In particular, very few genes affect one trait alone. Most genes have influences on many traits. Some traits, both behavioural and medical (such as susceptibility to heart disease), seem to be influenced – in ways that are imperceptible gene by gene, but detectable when their effects are added up – by most of the genome. That’s why the popular notion of a “gene for” some behavioural trait is misguided. In fact, it means that there may be no meaningful “causal” narrative that can take us from particular genes to behaviours.

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This is precisely why we need to resist seductively simple metaphors in genetics: blueprints, selfish genes, “genes for”. Of course, science always needs to reduce complex ideas and processes to simpler narratives if it is going to communicate to a broader audience. But I’ve yet to see a metaphor in genomics that does not risk distorting or misrepresenting the truth, so far as we currently know it. Fortunately, I do not think this matters for talking about the roles of genes in making a human. We will deal with those roles as they arise, without resorting to any overarching story about what genes “do”.

I haven’t even told you yet the worst of it, though. It’s not simply difficult to articulate clearly what, in the scheme of growing humans the natural way, genes do. For we don’t exactly know how to define a gene at all.

This isn’t a failure of biology, but a strength. It’s tempting to imagine that science can’t be fully coherent if it can’t define its key terms. But the most fundamental concepts are in fact almost invariably a little hazy. Physicists can’t say too precisely or completely what time, space, mass and energy are. Biologists can’t say what a gene or a species is. For that matter, chemists aren’t fully agreed on what an element or a chemical bond is. In all cases, these terms arose because it seemed as though they had a very specific meaning, but when we looked more closely we found fuzzy edges. Yet the reason we coined the terms in the first place was because they were good for thinking with.

That remains true. A gene is a useful idea, perhaps in much the same way as words like “family” and “love” and “democracy” are useful: they are vessels for ideas that enable us to have useful conversations. They are usually precise enough.

Here, then, is a definition good enough to let us talk about genes in the role of growing a human from cells. Think of a gene as a piece of DNA from which a cell is able to make a particular molecule, or group of molecules, that it needs in order to function. By passing on copies of genes, cells can pass on that information so that the progeny doesn’t have to rediscover it from scratch.

If you raised your eyebrows at “so that”, good for you. In such phrases, biology is given a false purpose, an illusory sense that it pursues goals. It is nigh on impossible to talk about biology – about growth, development, evolution – without some mention of aims. Try to remember that this is always mere metaphor. The way that the laws of the physical world have played out on our planet is such that entities called cells have appeared that have a propensity to pass on genes to copies of themselves. This is remarkable and marvellous. No one really understands why it happens – why reproduction, inheritance and evolution is possible – and that’s why we find it necessary to tell stories about it. All we can say is that there is absolutely nothing that forces us to invoke any supernatural explanation for it. The gaps that remain would make an extremely peculiar shape into which such an account might be squeezed.

Here’s another thing worth knowing about genes: a gene on its own is useless. It can’t replicate,10 it can’t even do the job that evolution “appears” to have given it. Frankly, there is no real point in calling a gene on its own a “gene” at all: the name connotes an ability to (re)produce, but a lone “gene” is sterile, just a molecule that happens to resemble a part of the DNA in a chromosome. It’s common to say that a gene is a piece of DNA with a particular sequence, but the truth is that such a physical entity only becomes a gene in the context of a living system: a cell, at minimum. Genes are central ingredients of life, but by the time you reach the level of the gene there is nothing left that is meaningfully alive.

No, life starts with the cell. And that’s why a gene only has meaning by virtue of its situation in a cell. Does this, then, mean that the cell is more fundamental to biology than the gene? You might as well ask if words are more fundamental to literature than stories. It is “stories” that supply the context through which words acquire meaning, making them more than random sounds or marks on paper.

And by “context” here I don’t just mean that a gene has to be in a cell in order to represent any biologically meaningful information. I mean also that, for example, the history of the cell, and of the entire organism, might matter to the function a gene has. A gene that is “active” at one point in the organism’s growth might represent a quite different message – have a different implication – than at a later or earlier point. Yet the molecular machine (the protein) encoded by the gene may be identical in the two cases. The gene doesn’t change, but the “instruction” it represents does.

You might compare it to the exclamation “Stop it!” Is that an instruction? Well, of course you don’t know from that enunciation alone what it is you are supposed to stop, but perhaps you might regard it as a generic instruction to desist from the activity you’re engaged in. But what if you hear someone shout “Stop it!” as you see a football rolling towards a cliff edge? Is that an instruction to desist in anything, or on the contrary an injunction to action? You need to know the context.

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The gene-centred narrative of life is just one example of our urge to somehow capture the essence of this complicated, astounding process – to be able to say “life starts here!” Science’s reductionist impulse gets a bad press, but breaking complicated things down into simpler ones is a tremendously powerful way of making sense of them. I think that what many people who complain about reductionism are reacting against is not so much this process of analysis – of taking apart – in itself, but the tendency then to assert “this is what really matters”. Science has sometimes been a little slow to recognize the problem with such assertions. When one group of physicists started insisting it was going to find a Theory of Everything – a set of fundamental laws from which the entire physical universe emerged – others pointed out that it would be nothing of the kind, because it would be useless in itself for predicting or explaining most of what we see in the world.

It’s not just that we should resist the temptation to see reductive analysis as a quest to identify what is more important/fundamental/real in the world. Sometimes the phenomenon you’re interested in only exists at a particular level in the hierarchy of scale, and is invisible above and below it. Go to quarks and you have lost chemistry. With genes and life it is not quite that extreme – but at the level of genes you are left with only a rather narrow view of some of the entities and processes that underpin this notion we call “life”. Life remains a meaningful idea from the macro level of the entire biosphere of our planet right down to the micro level of the cell. Within those bounds it encompasses a whole slew of factors: flows of energy and materials, the appearance of order and self-organization, heredity and reproduction. But below the level of the cell, you’ll always be overlooking something vitally important in life. As Franklin Harold has put it:

Something is not accounted for very clearly in the single-minded dissection to the molecular level. Even as the tide of information surges relentlessly beyond anyone’s comprehension, the organism as a whole has been shattered into bits and bytes. Between the thriving catalog of molecules and genes, and the growing cells under my microscope, there yawns a gulf that will not be automatically bridged when the missing facts have all been supplied. No, whole-genome sequencing won’t do it, for the living cells quite fail to declare themselves from those genomes that are already in our databases … The time has come to put the cell together again, form and function and history and all.

It is precisely the multivalent, multiscale implication of the word “life”, too, that creates the tensions, ambiguities and ambivalences about what it means to “grow a human”. We are thereby “making a life”, but not “making life”. That same truth is spoken in jest in a cartoon by Gary Markstein in which two white-coated scientists contemplate IVF embryos. “Life begins at the Petri dish!” exclaims one embryo; “Cloning for research!” demands another. “Even the human embryos are divided”, sighs a scientist.

This is the struggle we face in reconciling our notion of life as human experience with the concept of life as a property of our material substance. We are alive, and so is our flesh. While those two visions of life were synonymous, we could ignore the problem. Having a mini-brain grown in a dish from a piece of one’s arm tends to make that evasion no longer tenable.

It’s no wonder that different cultures at different times have had such diverse attitudes to the connection between the human body in utero, forming in hidden and mysterious fashion from something not remotely human-like, and the human body in the world. The insistence by some people and in some belief systems that “life begins at conception” is a modern utterance, often claiming firm support from the very science that in fact shows how ill-defined the idea is.

But the tension is an old one, as demonstrated by preformation theories of the human fetus. This was an anthropomorphization of the cell as explicit as that in cartoons that attribute voices and opinions to human embryos in petri dishes. Intuition compels us to look for the self in the cell. An insistence on locating it instead in our genes – as cell biologist Scott Gilbert puts it, to see “DNA as our soul” – comes from the same impulse. Perhaps we must be gentle in dispensing with these superstitions. Aren’t old habits always hard to shake off?

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.

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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.