The century of the gene

When the Human Genome Initiative published its first findings in 2002, the world was shocked. Genetic biologists, however, had long ago come to realise that DNA sequences are only part of the story of how organisms develop.

DNA Sequence chromatograms produced by automated sequencing machines. Credit: Mark Harmel / Alamy Stock Photo.
DNA Sequence chromatograms produced by automated sequencing machines. Credit: Mark Harmel / Alamy Stock Photo.

This essay originally appeared in ‘Consciousness, Genetics and Society: Perspectives from the Engelsberg Seminar’, Bokförlaget Stolpe, in collaboration with the Axel and Margaret Ax:son Johnson Foundation, 2002.

Fuelled by the expectation that knowing the sequence of our DNA would tell us who we are, US funding agencies launched one of the most ambitious scientific efforts of all time in 1990. I refer, of course, to the Human Genome Initiative. Since then, the pace of that effort has been furious:even before the decade was over, the finishing line was clearly in view. When in February 2001, two rival teams announced the results of their first analysis of this invaluable information, their report made front-page headlines around the world. Humans, it seems, have far fewer genes than had been expected — in fact, only a third more than the lowly roundworm. How can this be? And what does it mean? Are we really so similar to, and so little more than, mere worms? News of the extent of our commonality with all living species is as stunning as it is humbling. But at the same time, it invites a certain incredulity — and that not merely because of human pride. Simple observation of the manifest diversity of life also makes us resist, for it is impossible not to wonder: what is it, if not the number (and in many cases, even the structure) of the ‘genes’ encoded in our DNA that accounts for the extraordinary differences among living organisms? For the answer to this question, it seems that we will have to look to the regulatory dynamics that determine how the sequence information of the DNA is to be used by the cell. Here, in the complex regulation of genetic transcription, of translation, of protein structure and function, is where we will find what makes us human beings rather than worms, flies or mice. Knowledge of the sequence of our DNA can tell us an enormous amount, but it can almost certainly not tell us who we are.

But not everyone was taken aback by this news. While readers of the popular press may have been stunned, few biologists working at the frontiers of research in molecular genetics were astonished. True, they had expected a larger number of human ‘genes’, but they had long ago come to realise that DNA sequences are only part of the story of how organisms develop, and even of what we mean by a ‘gene’. They recognise, for example, that the spatial and temporal patterns of expression of a gene are even more crucial to the specification of an organism than the structure of that ‘gene’ is. They also know that no single definition of this word ‘gene’ can suffice. Of the many different definitions that are required to make sense of current usage, two stand out with particular clarity: one referring to a particular region of the DNA, and another to the unit of messenger RNA that is used in the synthesis of a particular protein. The number of genes of the second kind is in fact very much larger than that of the first kind (current estimates suggest more than ten times as many), for the fact is that many different ‘genes’ can be constructed out of a single specified region of the DNA. Because the particular context in which they use the word makes its meaning quite clear, ambiguities in usage rarely create problems for practising biologists. Not so, however, for most readers. Outside the laboratory, such linguistic uncertainties can lead to both confusion and misunderstanding — not only around the question of how many genes we have, but also of what genes are made of, where they reside, what they do and, perhaps most important, what genes are for.

The good news is that research in genetics has never been more exciting, and over the last few decades both the depth and the breadth of our understanding of the nature of genetic activity have grown spectacularly. With each advance, the picture of the role of genes in development that biologists learn to draw grows ever more complex and sophisticated, and in ever more conspicuous defiance of the simple mantra with which they began. The word ‘gene’ does not begin to do justice to the ingenuity of the mechanisms required to put biological organisms together — no more than the concept of the neuron does to the ingenuity and dynamic complexity of neural organisation, and no more than talk of individual minds to the complexities of language and cognition.

On each of these levels — in genetics, in neuroscience, in human behaviour — we have begun to confront what, from a philosophical point of view, appears to be essentially the same problem, namely, the inadequacy of a static, entity-based ontology for describing systems as complex as those we find in biology. Not only do we need to move from genes to gene networks, from neurons to neural networks, and from individual minds to social networks, but also we need a language that can capture the kinds of features that emerge from the interaction dynamics of these networks. Through sophisticated technologies, scientists in genetics, neuroscience and child development have acquired access to the dynamic interactions that not only bind their various constituent parts into wholes, but equally reveal the ways in which those interactions constitute the parts themselves. As a consequence, more and more scientists have begun to challenge traditional priorities.

For example, in neuroscience, where the fixed structure of the neuron, with its distinctive properties, has historically served as the primary unit of that science, today’s experts are turning their attention to the dynamics of synapses and synaptic structures. Brain function, we learn, is to be found in the neuronal connections (forged in part by experience) and in the temporal dynamics of the signals that traverse those connections.Similarly, more and more students of the cognitive and emotional development of children are looking to the social dynamics that shape the emergence of the infant self and mind.

Imitation and reciprocity are seen to be key not only to the development of language and cognition but also to their evolution and, more generally, to the evolution of what we think of as the ‘individual mind’. Much the same can be said of con-temporary genetics. In particular, geneticists no longer look for biological function either in particular genes, or in the structure of DNA, but rather in the communication networks of which the DNA is part. Having all but abandoned their efforts to define the gene, their focus has begun to shift to the search for biological function in the cellular processes that employ the DNA as a critical resource for growth and adaptation – in the cross-talk between and among all the players of the cellular orchestra.

Perhaps Alfred North Whitehead was right after all: focusing on entities gives us the sort of reification that is fundamentally inappropriate to the study of living phenomena which are, at bottom, processes. Perhaps what we need then is a dynamic ontology to replace our static ontology — one that will enable us to avoid the pitfalls of such traditional and worn out questions as: which is primary, the chicken or the egg? Which is nature or nurture? Structure or function? Perhaps what we need is an ontology that allows us to ask a different sort of question altogether.

Evolution might be described as a machine that transforms function into structure, and over the long duration of time, it has produced inter-woven and hierarchical structures of biological organisation that leave even our most sophisticated engineers in awe. Because of their extensive and pervasive mechanisms of feedback, these structures have acquired both robustness and adaptability. But feedback occurs on every level, and many such processes never reach the level of genetic transcription (only for long-term effects is it necessary that they do so). And even when they do, it is in the dynamics of gene activation rather than the sequence of nucleotides that we are to find the principles of organisation and function.Because of the extraordinary interactivity biologists have been finding on every level of organisation, few adherents of simplistic genetic determinism can now be found. We are being forced by the most cutting-edge research to abandon traditional dichotomies between nature and nurture, and even between genetic and epigenetic. The secrets of biological development, just like those of cognitive development, are revealing the work of interaction all the way down.

The bad news, however, is that little of this new sophistication has yet to reach the public eye. Indeed, it now seems that the gap between public and technical understanding has reached something of a critical point, one that urgently requires attention. Two years ago, I wrote a book on The Century of the Gene in an effort to bridge the gap that has emerged. At the same time, however, I also intended my book to be a celebration of the research that has created such a gap, and of the increasing richness of our understanding of the role of DNA in biological development. My argument was that, because of the very prowess of molecular analyses of the cell, we have learned once again to marvel not at the simplicity of life’s secrets, but at their complexity.

Furthermore, I gave the Human Genome Initiative a great deal of credit for bringing us to this point. In revealing the sequence of our DNA, that project may not have succeeded in telling us who we are, but it has taught us how little we know. And that lesson, I suggested, may in the long run prove even more valuable. Yet its contribution does not end with hubris. The information it is producing will also give us tools with which to embark on a new era of biology. Perhaps, a hundred years down the line, our grandchildren will find themselves reading a book called The Century Beyond the Gene.


Evelyn Fox Keller