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

Fueled 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…

Unpacking the genome hasn’t turned out to be the master key to understanding life that many thought it would be– but that’s no reason not to celebrate what it does illuminate: “The century of the gene,” from Evelyn Fox Keller in @EngelsbergIdeas.

* Calvin, in Calvin and Hobbes (Bill Watterson)

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As we investigate inheritance, we might spare a thought for D’Arcy Wentworth Thompson; he died on this date in 1948.  A classics scholar who was also an accomplished biologist and mathematician, Thompson is best remembered for On Growth and Form (1917, new ed. 1942), a profound consideration of the shapes of living things, starting from the simple premise that “everything is the way it is because it got that way.”  Thus one must study not only finished forms, but also the forces that molded them: “the form of an object is a ‘diagram of forces’, in this sense, at least, that from it we can judge of or deduce the forces that are acting or have acted upon it.”

The book paved the way for the scientific explanation of morphogenesis, the process by which patterns are formed in plants and animals.  Thompson’s description of the mathematical beauty of nature inspired thinkers as diverse as Alan Turing and Claude Levi-Strauss, and artists including Henry Moore, Salvador Dali, and Jackson Pollock.  Peter Medawar, the 1960 Nobel Laureate in Medicine, called On Growth and Form “the finest work of literature in all the annals of science that have been recorded in the English tongue.”

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