James Fanu - Why Us? - How Science Rediscovered the Mystery of Ourselves

Both the Human Genome Project and the Decade of the Brain have indeed transformed, beyond measure, our understanding of ourselves – but in a way quite contrary to that anticipated.

Nearly ten years have elapsed since those heady days when the ‘Holy Grail’ of the scientific enterprise, the secrets of life and the human mind, seemed almost within reach. Every month the pages of the science journals are still filled with the latest discoveries generated by the techniques of the New Genetics, and yet more colourful scans of the workings of the brain – but there is no longer the expectation that the accumulation of yet more facts will ever provide an adequate scientific explanation of the human experience. Why?

We return first to the Human Genome Project, which, together with those of the worm and fly, mouse and chimpanzee and others that would follow in its wake, was predicated on the assumption that knowledge of the full complement of genes must explain, to a greater or lesser extent, why and how the millions of species with which we share this planet are so readily distinguishable in form and attributes from each other. The genomes must, in short, reflect the complexity and variety of ‘life’ itself. But that is not how it has turned out.

First, there is the ‘numbers problem’. That final tally of twenty-five thousand human genes is, by definition, sufficient for its task, but it seems a trifling number to ‘instruct’, for example, how a single fertilised egg is transformed in a few short months into a fully formed being, or to determine how the billions of neurons in the brain are wired together so as to encompass the experiences of a lifetime. Those twenty-six thousand genes must, in short, ‘multi-task’, each performing numerous different functions, combining together in a staggeringly large number of different permutations.

That paucity of genes is more puzzling still when the comparison is made with the genomes of other creatures vastly simpler than ourselves – several thousand for a single-cell bacterium, seventeen thousand for a millimetre-sized worm, and a similar number for a fly. This rough equivalence in the number of genes across so vast a range of ‘organismic complexity’ is totally inexplicable. But no more so thanthe discovery that the human genome is virtually interchangeable with that of our fellow vertebrates such as the mouse and chimpanzee – to the tune of 98 per cent or more. There is, in short, nothing to account for those very special attributes that so readily distinguish us from our primate cousins – our upright stance, our powers of reason and imagination, and the faculty of language.

The director of the Chimpanzee Genome Project, Svante Paabo, had originally anticipated that its comparison with the human genome would reveal the ‘profoundly interesting genetic prerequisites’ that set us apart:

The realisation that a few geneticaccidents made human history possible will provide us with a whole new set of philosophical challenges to think about … both a source of humility and a blow to the idea of human uniqueness.

But publication of the completed version of the chimpanzee genome in 2005 prompted a more muted interpretation of its significance: ‘We cannot see in this whywe are so different from chimpanzees,’ Paabo commented. ‘Part of the secret is hidden in there, but we don’t understand it yet.’ So ‘The obvious differences between humans and chimps cannot be explained by genetics alone’ – which would seem fair comment, until one reflects that if those differences ‘cannot be explained’ by genes, then what is the explanation?

These findings were not just unexpected, they undermined the central premise of biology: that the near-infinite diversity of form and attributes that so definitively distinguish living things one from the other must ‘lie in the genes’. The genome projects were predicated on the assumption that the ‘genes for’ the delicate, stooping head and pure white petals of the snowdrop would be different from the ‘genes for’ the colourful, upstanding petals of the tulip, which would be different again from the ‘genes for’ flies and frogs, birds and humans. But the genome projects reveal a very different story, where the genes ‘code for’ the nuts and bolts of the cells from which all living things are made – the hormones, enzymes and proteins of the ‘chemistry of life’ – but the diverse subtlety of form, shape and colour that distinguishes snowdrops from tulips, flies from frogs and humans, is nowhere to be found . Put another way, there is not the slightest hint in the composition of the genes of fly or man to account for why the fly should have six legs, a pair of wings and a brain the size of a full stop, and we should have two arms, two legs and that prodigious brain. The ‘instructions’ must be there, of course, for otherwise flies would not produce flies and humans humans – but we have moved, in the wake of the Genome Project, from assuming that we knew the principle, if not the details, of that greatest of marvels, the genetic basis of the infinite variety of life, to recognising that we not only don’t understand the principles, we have no conception of what they might be.

We have here, as the historian of science Evelyn Fox Keller puts it:

One of those rare and wonderful momentswhen success teaches us humility … We lulled ourselves into believing that in discovering the basis for genetic information we had found ‘the secret of life’; we were confident that if we could only decode the message in the sequence of chemicals, we would understand the ‘programme’ that makes an organism what it is. But now there is at least a tacit acknowledgement of how large that gap between genetic ‘information’ and biological meaning really is.

And so, too, the Decade of the Brain. The PET scanner, as anticipated, generated many novel insights into the patterns of electrical activity of the brain as it looks out on the world ‘out there’, interprets the grammar and syntax of language, recalls past events, and much else besides. But at every turn the neuroscientists found themselves completely frustrated in their attempts to get at how the brain actually works .

Right from the beginning it was clear that there was simply ‘too much going on’. There could be no simpler experiment than to scan the brain of a subject when first reading, then speaking, then listening to, a single word such as ‘chair’. This should, it was anticipated, show the relevant part of the brain ‘lighting up’ – the visual cortex when reading, the speech centre when speaking, and the hearing cortex when listening. But no, the brain scan showed that each separate task ‘lit up’ not just the relevant part of the brain, but generated a blizzard of electrical activity across vast networks of millions of neurons – while thinking about the meaning of a word and speaking appeared to activate the brain virtually in its entirety. The brain, it seemed, must work in a way previously never really appreciated – not as an aggregate of distinct specialised parts, but as an integrated whole, with the same neuronal circuits performing many different functions.

The initial surprise at discovering how the brain fragmented the sights and sounds of the world ‘out there’ into a myriad of separate components grew greater still as it became clear that there was no compensating mechanism that might reintegrate all those fragments back together again into that personal experience of being at the centre, moment by moment, of a coherent, ever-changing world. Reflecting on this problem of how to ‘bind’ all the fragments back together again, Nobel Prize-winner David Hubel of Harvard University observed:

This abiding tendency for attributes such asform, colour and movement to be handled by separate structures in the brain immediately raises the question how all the information is finally assembled, say for perceiving a bouncing red ball. It obviously must be assembled – but where and how, we have no idea .