Nature Beats Nurture
Nigel Hawkes / London Times 13feb01
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The genome project has discovered that we have only 10,000 more genes than a worm. Does this mean that our environment is more important than our genetic make-up? |
So long-awaited has been the publication of the human genome that it might easily have lost all power to surprise. Yet at the very last minute it has thrown us a curve ball. Instead of the 100,000 genes that most scientists had been expecting, the two rival versions of the genome published yesterday show that there are a mere 30,000. Such a modest parts list is a real shock — “the single most surprising fact” to emerge from the double publication, says Dr Craig Venter of Celera Genomics, who led the privately funded initiative.
In this — as in so many other things — the rival genome projects do not see entirely eye to eye. The public and charity-funded effort puts the number of human genes at between 30,000 and 40,000, while Celera comes up with a number between 26,383 and 39,114.
These numbers may differ, but they are in the same ball park. It means, says Venter, that it takes only another third as many genes to make a human being as it does to make a worm.
While this is humbling, it does not mean that the genes are unimportant. Nor does it have any real bearing on the old issue of nature and nurture, as some have suggested. The evidence that many characteristics, including intelligence, have a strong inherited component never rested on a presumption that human beings have many more genes than lower animals.
But the relative paucity of the genes does have implications for medicine, and for a deeper understanding of how human beings really function. It shifts the emphasis away from the genes and towards the proteins, the true working parts of the human machine.
Ever since the breaking of the genetic code in the 1960s, we have known that all living things are cut from the same cloth. That cloth is DNA — deoxyribonucleic acid — whose long molecules spell out in the sequence of their bases the recipe for making particular proteins.
The code is the simple way in which the bases, in groups of three, identify particular amino acids, which are then assembled in the right order to make a protein. The discovery that all creatures share the same code was a profound one, for it instantly made sense of evolution and reminded us that all life is one.
But such is our perception of ourselves as a higher form of life that this message has never really struck home. People have continued to believe that there is a step-change between the animals and us — and many expected that change to be manifested in the number of genes we carry.
Some have even suggested that the human brain alone would need 100,000 genes to explain its operation. That, it now appears, was a fantasy. If there is a qualitative difference between our brains and those of animals, it must lie in the proteins, not the genes. Most likely there is no qualitative difference at all, but simply a difference of size and the complexity of cross-links.
As happens so often in science, a peak is conquered only to reveal a still more daunting one ahead. Those who believed that elucidating the genome would provide the key to understanding everything will have to think again. The next peak is the proteome — a complete listing of the 250,000 or so proteins that the 30,000 genes are capable of making.
This will prove infinitely more complicated, because proteins can vary in health and disease, and have another clever trick up their sleeves — the long chains of amino acids do not string out like a washing line, but curl up on themselves in complex three-dimensional shapes that determine their properties.
A miscurled protein is responsible for Creutzfeldt-Jakob disease (CJD), and probably for many other human and animal diseases. So, ahead lies the task not only of listing the proteins, but also of understanding how they change in disease, and of how they fold, which has been called the greatest unsolved problem in biology.
In the wake of yesterday’s publication, both teams were playing down the importance of the genes in human affairs — as if passing the winning post has made the race seem almost an irrelevance. “Those who are looking for forgiveness of responsibility for their own lives in the genetic code will be very disappointed,” says Venter. “Most of biology happens at the protein level, not the DNA level.”
The relative paucity of human genes should not really have come as such a surprise, because it was already known that the number of DNA bases carried by different species varies hugely. Human beings have 3.1 billion “base pairs” — of which only about 1 per cent are actually parts of working genes — but the lily has 91 billion.
Until now, these differences were attributed to the amounts of “junk” DNA that accumulates in the genome — fragments of no-longer useful genes, or simply repeated patterns of base pairs that have parasitised the genome and used it as a way of reproducing themselves. Now it seems that this was only half the answer. The fact that the human body needs so few genes is likely to have some worrying implications for medicine, which had hoped to find easy genetic answers to disease, and simple explanations for the different ways people respond to the same drug.
“The drug industry has been saying ‘one gene, one patent, one drug’,” says Venter. “But the uses for this approach can be counted on the fingers.”
To him, this finding is gratifying because it means that patents on genes are far less valuable than they once seemed. His company, Celera, has been strongly criticized because it had kept open the option of patenting some of the genes it had found, which the publicly funded effort claimed would block off whole fields of activity to others. “Because of the relatively low number of genes, Celera scientists believe it will be necessary to look elsewhere for the mechanisms that generate the complexities inherent in human development,” the company said in a statement yesterday.
“It’s kind of humbling, isn’t it?” says Ari Patrinos, of the US Department of Energy, which funded much of the public effort. “There are very, very few traits or diseases that are monogenic (caused by a single gene). It has been an emerging consciousness over the past five years — the recognition that our genes don’t control everything.”
But does the finding mean that heredity is less important in human affairs than was previously supposed? For decades the argument has raged over whether nature or nurture is the more important in determining human qualities. So tied up is this argument with political and ethical beliefs that it is often difficult to disentangle fact from prejudice.
But the evidence is strong that heredity does matter. It does not come from studies of the genome, for despite some claims, nobody has much idea which genes have anything to do with specifically human qualities such as general intelligence. It comes, rather, from studies of identical and non-identical twins, a perfect test-bed for distinguishing the effects of nature from those of nurture. Identical twins raised apart are far closer in IQ than are non-identical twins, leading to the conclusion that about half the differences in IQ between individuals can be accounted for by heredity.
These studies are in no way affected by the genome project, because they rest on different foundations. All that the new finding tells us about them is that clearly there are not thousands of genes labelled “IQ” that are carried by the fortunate but not by the rest of the population.
We might already have guessed that, because the chimpanzee shares more than 98 per cent of human genes. If genes alone really were the key, those few that we do not share would have to have accounted for the big gap between human and ape intelligence.
According to Sir John Sulston, a former director of the Sanger Centre near Cambridge and a leading player in the publicly funded genome initiative, the difference lies not in the number of the genes, but in their mode of action. Higher creatures have more control genes, enabling them to play subtler tunes on the basic set of ordinary genes which are universally shared.
According to the historian and philosopher Thomas Kuhn, science advances when a new revolution, or paradigm, takes hold of the scientific consciousness. Such paradigms are often great simplifications, such as plate tectonics, which instantly made the whole of geophysics comprehensible.
But between these shifts of scenery, science advances by the accumulation of detail. The discovery of the structure of DNA and the genetic code was a paradigm shift that had the effect of making the whole of genetics seem simple. Now we are learning what we always do: that it was not as simple as that after all. The never-ending fascination of science is that every question raises another, and that nature always has fresh complexities to throw at us. The unveiling of the genome is not an end, but a beginning.
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