Things I wish I’d read before finishing The Hidden Half… #17

A brilliant account of an innate hidden half from a neurogenticist suggests that the genetic ‘blueprint’ is seriously fuzzy.

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Innate– How the Wiring of Our Brains Shapes Who We Are – Kevin Mitchell. October 2018. 

In the endless nature/nurture dogfight, it sounds from the title of Kevin Mitchell’s superb book as though he’s one of nature’s Rottweilers.

But not so fast. Although he readily agrees that genes play a powerful role – that much is obvious, he says, and I’ve no doubt he’s right – we’re not being invited here into any simple allegiance. Expectations of a deterministic account of how people turn out, based on whatever we inherit from our parents, will be disappointed. In other words, this is no claim for a ‘blueprint’. It is, in fact, evidence against a blueprint. 

The fuzziness that Kevin adds to the genetic instruction manual comes from a large element of randomness in human development. This has nothing to do with whatever we acquire from our parents. The random element appears for all practical purposes spontaneously, in each of us. But it is nevertheless innate. 

At heart, it’s a simple observation, though with fascinating implications. Human differences which are innate in origin do not have to be genetic. When the two words – ‘genetic’ and ‘innate’ – are often used interchangeably, that might sound confusing. But innate development, he argues persuasively, is partly inherited and based on genes, but partly a roll of the dice. It’s just that the dice are rolled on the inside too.

‘There is noise in all the operating parameters of every cell – in the concentration of every component, in the flux of every reaction, in the state of every control system.’

Kevin Mitchell

Nature does this simply because it must. The biological processes that govern our development are infinite, and – here’s the critical point – the genetic programme that directs them is bound to be imperfectly applied (unsurprising, given the complexity). As a result, there is often no simple and reliable line of determinism from genotype to phenotype (how the person turns out). We are, all of us, the partial product of noise from before birth. And not a trivial amount of noise either.  

It’s all because…

At the most simple end of genetics, a few single-gene diseases are a matter of certainty: if you have the gene, you have the illness; if you don’t, you don’t. Genes in these cases are deterministic. But at the other end of the spectrum, there is a hefty slice of unpredictability in how we turn out. And also a hefty slice of uncertainty about how we got here. We can’t see it coming, and we can’t see where it came from. It is fundamentally untraceable and cannot be identified genetically – even though it might still be innate in origin.

Appealing to what he calls the geneticist’s version of Murphy’s Law (‘if it can go wrong it will,’ adapted to become: ‘if it can vary, it will’), he describes the strong forces for inconsistency of genetic expression, not through any particular mechanism, but through the necessary variability and fallibility of all the various mechanisms. In a system that large and complicated, what do you expect but chance differences, errors and mere probabilities? Even small changes in temperature can affect the way a neuron develops. We know this. We can see it. We just can’t tell what overall effect it will have. The genome is a plan, he says, not the building; and a lot of extraordinarily-detailed, biological construction-work goes on between one and the other, entailing a mass of uncertain outcomes.  

The argument is captured by that gorgeous notion that you can’t bake the same cake – twice; you can’t run the same process when it’s that complicated and expect it to turn out the same each time. We see this in ‘identical’ twins. I talk a little in The Hidden Half about unexplained behavioural and physical differences in identical twins, and even the differences we see between two halves of the same person. Kevin points out that such differences also exist in the physical structure of the brains of identical twins, and even in the two halves of the brain of one person, despite sharing identical genes. 

The genome’ he writes, ‘cannot predict (and cannot specify) any cell’s exact state – certainly not every cell’s exact state. There is noise in all the operating parameters of every cell – in the concentration of every component, in the flux of every reaction, in the state of every control system.

‘Now, you might think all that might not matter very much at the level of the whole cell, but actually that noise can percolate through the whole system and manifest in big fluctuations at the level of things that cells really do care about, like gene expression.’ 

Such fluctuations in gene expression can have surprisingly large effects, he says. 

Innate and The Hidden Half

His account is consistent with The Hidden Halfin this respect: that the process of human development is bound to contain a substantial chunk of enigmatic or hidden variation. In other words, there is also an innatehidden half. 

But he differs significantly in his emphasis. Whilst I agreed in the book that a large, innate, random developmental variability was possible (I say somewhere that randomness in gene expression could be part of the explanation for human difference and acknowledge at least one researcher in the field who thinks so) my own examples in the relevant chapter focus more on potential external influences. Kevin simply doesn’t need these to reach his conclusion that there are large randomising effects on human behaviour (although I still think the environment has a randomising part to play). There’s abundant unpredictable variation to be found in biological and brain development alone. 

If I’d known Kevin’s work earlier, I’d certainly have drawn on it to talk more about what some call ‘the gloomy prospect’ from both outside and in (the gloomy prospect states, roughly, that we’ll never pin down a large proportion of the causes of human difference because they are not systematic and thus do not yield to research – which is what makes some researchers gloomy – but are unshared and stochastic or chance in nature). The fascinating bottom line that I would have taken gratefully from Kevin’s book to add to my own is that the gloomy prospect/hidden half applies to a large part (clearly not all) of both the innate and external causes of human difference. Genes are not a hard-rock alternative to what I call enigmatic variation; they are part of a system that necessarily entails enigmatic variation.  

Kevin brings the expert’s understanding – he’s an academic neurogenticist – to bear on explaining the wonderful mechanisms by which enigmatic variation muddies the innate part of the system. I hope he won’t mind my suggestion that what he and I have in common is a resistance to excessive determinism from known or identifiable causes. He also goes on to say that innate does not – of course it does not – mean we should shrug our shoulders and give up trying to do anything for people. Innate is not the same as predictable, consistent, or beyond influence – all of which is a useful counter to the reductive arguments that sometimes fly around elsewhere.

There’s lots more. Just read it. It’s brilliant. 

Kevin Mitchell tweets @wiringthebrain

He has a webpage: kjmitchell.comParagraph

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