How many different words did Shakespeare use? Google tells me: 31,534. How many letters did Shakespeare use? 26 – including, if my memory serves me: “Thou zed, thou unnecessary letter!” So it’s not the number of letters which counts; it’s what you do with them.
This consideration must have consoled the scientists who attempted to estimate the number of genes in the human genome. Someone started with a splendidly exaggerated figure of more than six million. But that rapidly came down to more realistic figures during the 1990s, to a final 23,000 or so, when the genome was finally mapped at the turn of the century. It was a surprisingly small figure to be the complete code for human complexity. Given that a chicken has about 16,000 genes and a grape about 30,000 we may guess that the exact number is not the point.
But then genetics have always been surprising. It was a surprise when good Fr Mendel’s experiment with peas demonstrated that inherited characteristics were not a blend but were transmitted by discrete entities. It was a further surprise when these entities resolved into four letters: A, G, C and T, repeated in a different order over and over again: just four different letters needed to describe life. And a surprise to me to learn that every cell in our bodies contains as many as three billion base pairs. And if all the information carried by just one of these letters were written out it would require a book of 1.5 million pages. All I can say is: Phew!
But there were more surprises yet to come. The mapping of the human genome was a moment of great promise. It would only be a matter of time before we discovered the holy grail of identifying the genetic errors which cause human disease, and correcting them. Or the less holy grail of discovering how to bless our progeny with all the finest characteristics. The ultimate version of our family: homo sapiens artificialis, was only just over the horizon. Except that he wasn’t. It was gradually discovered that the regulatory elements used genes and clusters of genes in extremely complex ways. It was surprisingly hard to detect direct cause and effect. This could sometimes be usefully achieved in some discrete instances, but it became clear that nirvana was further off than we thought.
The situation was complicated by non-genetic regulators which were attached to genes – it would seem as a result of the organism’s experience – and which could to some extent be inherited. The last decade has been important for epigenetics, as this science is called. Interestingly, this has shown that the French naturalist Lamarck’s theory of the heritability of acquired characteristics still has something to contribute to our understanding. The programme of research ahead is formidable.
And that is only the start. The proportion of the genome known to be active was about three per cent. It was assumed that the far greater part was just surplus. But a major report on this “junk” DNA, published this September and known by the acronym ENCODE, tells us that 80 per cent is biochemically very active indeed. The problem is that we don’t yet know what it is active at. It may be a huge part of the regulatory procedure, or it may just be surplus duplication or abandoned in our long evolutionary history. If the former, it is a prize. If the latter, it will exhaust many resources to no useful end. One scientist in the project simply described the DNA as a jungle.
But although only about three per cent of DNA encodes proteins, frustratingly, much of human disease is associated with the non-coding areas of which we have known little until now. Will ENCODE at last lead us to mastering heritable disease?
Given the surprises so far, I would be foolish to forecast the future, but I can make a stab at some of the moral questions which will exercise us. First, our long-established habit of deducing moral imperatives from structure will have to survive our acceptance that God created our structures indirectly and dynamically through evolution. Thus, for example, the human fertility rate, developed during quite different conditions, is about four times as high as is required for population replacement in developed countries. How would we lawfully correct this accidental maladaptation? Related to this are the problems which can arise from both over-fertility and under-fertility: gross changes in fertility rates tend to create serious age imbalances in populations.
A second, contemporary question is the use of mitochondrial DNA from a third person, in order to avoid mitochondrial disease in a conceptus. Mitochondria is not personal genetic material; it is descended from a bacterium and is concerned with cell functions. The suggestion that the conceptus will have three parents owes more to rhetoric than reality. Subsidiary moral questions arise: potential need for additional conceptions, leading to the death of unused embryos; interference with the natural conduct of intercourse (see previous paragraph); and the extent of our rights to manipulate conceptions. While all of these might arise in any one case, the moral issues fundamentally differ.
Behind this lies a large question: what are the proper limits to our lawful interference in the genome? The issues of curative genetic manipulation raise different questions from the provision of “desirable” characteristics such as intelligence or an extra inch or two of height. We can have no doubt from the current use of eugenic abortion to ensure a child of a wanted sex that this will be a live issue. We shall need very clear heads.
If you would like to look more deeply at the ENCODE project, try http://www.nature.com/encode/#/threads. I suggest that you start by looking at a short video on that page, titled Voices of ENCODE.