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Today we are developing a science that could change the world – for good or ill – more profoundly than ever before. This science of genetics promises – or threatens – nothing less than the creation of life.
Colin Tudge leads the reader gently through the deepest intricacies of genetics. He traces its history. He explores its awesome power and its current applications. And he speculates on its thrilling – or terrifying – future. He has written an essential book for anyone interested in the future of the human race.
Cover
About the Book
About the Author
Title Page
Prologue
1 The Puzzle of Heredity and the Idea of the Gene
2 The Reality of the Gene
3 And After Many a Summer
4 The Games Animals Play
5 Sex
6 Breeding
7 The Age of Genetic Engineering
8 Conservation, Evolution and Murder Most Foul
9 The Improvability of Man
10 A New Created Life
11 Sense and Sensibility
Copyright
Colin Tudge was educated at Dulwich College and Peterhouse, Cambridge. For nearly three decades he has written on biological issues for magazines and newspapers such as New Scientist and the Independent, and during the 1980s he presented his own science programme on BBC Radio 3. His previous books include The Famine Business, Future Cook, Food Crops for the Future, The Food Connection, Global Ecology and Last Animals at the Zoo. He is the only three-time winner of the Glaxo Science Writer of the Year Award and both Last Animals and The Engineer in the Garden were shortlisted for the Rhône-Poulenc Science Book Prize.
A woman of no great age – just 120 or so – reaches from her balcony a quarter mile above the ground, brushes aside the snow, and picks from the ivy that clothes the building to the eaves, a ripe passion fruit. It is the scarlet variety – a touch of colour – almost seedless, and big as a pomegranate. Hers is a pleasant and typical urban existence; the high-rise apartments all around like cliffs and spires of green, dotted here and there with fruit that once grew only in the tropics; deer in the gardens; eagles and kites overhead; the occasional wolf, yelping in the forest on the city edge.
You may or may not find such a vision pleasing: too fanciful, perhaps; too artificial; or too smug. It is a matter of taste. You will surely prefer it, though, to another which perhaps is more likely: a desert that stretches through almost all of Africa; a rising sea that has already obliterated lowlands everywhere, from the arable fields of eastern England to the entirety of Florida; fragments of humanity under siege, desperately clinging to what they have left, spawning committees, throwing up despots, and inventing religions to fend off and to explain to themselves the horror that has overtaken them.
Or indeed – for futurism is a game that anyone can play – you might care to envisage a thousand and one scenarios of your own: of life much the same as now; of life that contrives to be the same as now, but in which there are two, or three, or five times as many people; of life like now but with half the houses empty; like now but with no animals, or wild plants; or so radically different from the present as to beggar belief – with people living effectively for ever, and dinosaurs in zoos, and the world cleaned up (or nibbled away) by life-forms reinvented, and without precedent in the history of the Universe. All that is certain is that almost any future you care to envisage could in theory come about. Provided you do not choose to reinvent the laws of physics, which seem to be beyond transgression, anything you can bring to mind could probably be achieved.
Or rather – any future you may care to bring to mind could overtake us: for we, the British, the Americans, the Australasians, the Africans and the Asians – we the human species – are not in control. We aspire, or many of us do, to live in democracies. Even despots love the word ‘democracy’. In the name of democracy, we hold protracted and immensely expensive elections. Of course this is worthwhile, for some governments are clearly less disastrous than others.
But even the world’s most committed democracies have a quality that is merely cosmetic; because, in the end, the lives of individual people, and the destiny of humanity as a whole and of our fellow species, is only in part – only in superficial part – determined by governments, elected or otherwise. For at least two million years, since human beings first began seriously to develop technologies, our individual lives and our overall fate, even our evolution, has largely been shaped by those technologies; and in the main those technologies have effectively followed their own logic. One idea has led to another, and each new idea has shaped society afresh. Governments, kings, emperors, like the rest of us, have for the most part merely adjusted to what had become available. Nobody has truly determined the course of events. The most successful have been those who have adjusted fastest to whatever new technique is most powerful.
So long as the technologies were feeble, and so long as human beings were a rare and scattered species, this laissez faire attitude to our own ingenuity mattered very little. But the technologies soon became very powerful; and because of that, we soon ceased to be rare and scattered. Our ancestors had fire, a million years ago. It is truly amazing what can be achieved with a stone axe and a bone-tipped spear. Within the past few tens of thousands of years, it seems, our ancestors obliterated vast suites of other animals, including the big herbivores of Europe and North America and the sabre-tooths that preyed upon them. A few thousand years ago, before the Romans came, ancient Britons de-forested much of Britain, and created the modern moors and heaths. The beautiful but stark islands of the Mediterranean were forested until a few thousand years ago. There was never a policy to bring about such vast and permanent ecological change. It was just the way things turned out, as our ancestors followed their noses, exploited the tools they had to hand, made new ones, and solved their day-to-day problems. The technology employed was of the kind that now looks so quaint in local museums. With stone axes and an aptitude for fire our ancestors altered the entire world, long before any of today’s societies – or any of those in written history – had come into existence.
We have come a very long way since the stone axe. We have not simply created vastly better technologies. We have devised quite new ways of creating technologies. We no longer rely simply upon ingenuity and common sense. For the past several thousand years, at least, many kinds of philosopher have practised what may loosely be called ‘science’; and in the past 300 years, in the western world, the sciences have been refined into a series of disciplines, and of methods, which produce deep and more or less certain insights into the mechanisms of the world and which, increasingly, far transcend common sense. Out of this new science has come a new species of technology which can properly be called ‘high-tech’; the kind of technology that cannot be created, or even conceived, without the extra insights of formal science. ‘Ordinary’ technologies, which relied simply upon human invention, were powerful enough, and still predominate in everyday life. They embrace even the steam engine, which in its earliest forms involved no bona fide science at all. But when science and technology work in harmony – each feeding upon, and developing the other – the combination is very powerful indeed. The resulting machines are stunning; to date, the microchip is perhaps the apotheosis. The effect of high tech upon the world at large is commensurately huge. The rate of change outstrips the transformations that our ancestors brought about, a hundred or a thousand fold.
Now we are busily developing a science, and a resultant group of high technologies, that could change the world and our attitude to it more radically than any we have seen before: the science and technologies of genetics, and in particular of what has been called (I believe misguidedly) ‘genetic engineering’. As I hinted above, the science and technologies promise – or threaten – nothing less than the creation of life, or the indefinite prolongation of the life we already have.
If this science and these technologies are deployed adroitly, they could do more than any other sciences or techniques to solve our present problems, and avert the pending disasters of the future. More than any other science, they could help us to provide agricultures that can feed ten billion people, but do so humanely and without destroying the rest of the environment. They could provide methods of manufacture that preserve fossil fuels and reduce, or even reverse, the pending greenhouse effect; and transform the economies of present-day ‘Third World’ countries, and truly help to create a new ‘world order’. They could provide us with medical techniques that could defeat most infections within a century from now, and probably begin a serious attack upon the cancers while at the same time providing benign but certain methods of contraception that at last will enable people to regulate their own families as so many obviously want to do, even if they have no money or access to high-flown clinics. For the conservation of animals and plants, the science and high technologies of genetics are already vital. Without their adroit application, we cannot hope to save more than a token proportion of our fellow creatures from extinction. On the other hand, if we fail to remain in control, then the science and the new technologies could equally be employed for ends that we may well consider evil, or at least deeply sinister; and which, if things go wrong, could trigger a chain of biological destruction that could outstrip any we have seen before.
As things are, there are two prime reasons why we cannot hope to deploy science and technology astutely; to seize what is there to be seized, and avoid the potentially horrendous side-effects. First, we simply have not defined what it is we want to achieve. We still have the attitudes of the new stone age; that is, we are still content merely to follow our noses. Later in this book I will discuss the notion of natural selection, and explore its deep flaw, which is that natural selection does not look ahead, and in general is bound to favour short-term advantage over long-term. Our stone-age ancestors did not plan, they evolved, according to natural selection. If we simply do as they did, we are bound to accumulate long-term problems, and if we do not address them, they will become overwhelming. In fact, the ecological ills of the world which have now become such a cliché represent, in large part, the accumulated side-effects of 10,000 years of agriculture, along with another 500,000 or so of over-efficient hunter-gathering. But, except for the occasional world conference, where politicians compete for a few days to appear far-sighted, world politics as practised is not distinguished by any particular sense of direction. In general, we do what is there to be done, as our Cro-Magnon ancestors did, and then adapt as best we can to whatever new circumstances we happen to have created.
Second – which is closer to the subject of this book – we cannot hope to deploy science and technology for the public good in the foreseeable future because, quite simply, science and high tech are not in the public domain. People talk about all kinds of things, from football to opera, from sex to politics, but only professional scientists commonly talk about science. To be sure, this is far more true in Britain than in many other countries. In Britain, indeed, educated people still take a pride in not knowing any science. The term ‘intellectual’ is still reserved for those whose learned discourse is confined entirely to literature. The mood is changing slightly, but until very recently (and certainly when I was at University) scientists were considered an odd and slightly dangerous bunch, and professors of physics who were foolish enough to reveal what they did for a living at cocktail parties were likely to spend the rest of the evening talking to the potted plants. We live in a society dominated by science and technology, but we do not live in a science ‘culture’. Science and technology are treated not as a flowering of human creativeness, subject to human frailty, but like the weather: a fact of existence, beyond our control.
Indeed – in Britain at least – science and what are vaguely termed ‘the humanities’ are loosely divided into what C.P. Snow in the late 1950s called ‘the two cultures’, and the schism between the two is deep and pernicious. In the century in which science and high tech have made their greatest impact, and brought the world to a point of departure that may be terminally destructive but could still be idyllic, most people have remained unaware of most of the changes and the new ideas, and the people who are acknowledged as intellectual leaders take a positive pride in not understanding the source of the most significant change.
Yet without understanding, there can be no control; or at least none of the fine and subtle kind that is now required. Furthermore, the necessary understanding requires more than the passing of exams, for science and the high technologies that spring from it can be deployed adroitly only when science has become a natural and accepted part of our culture. It is not simply a ‘method’ for exploring the material facts of the Universe: its ideas change the way we look at all of life. Science must indeed be placed within broader contexts: integrated, in so far as this is possible, into all aspects of philosophy, including economics, politics, ethics, aesthetics, and indeed into religion. The point is not to put science on a pedestal, so that all other disciplines may pay homage, but to bring science and the high technologies that it generates back under human control; or rather, to begin to exercise control for the first time in our very long history.
The purpose of this book is to contribute to the scientific culture, and to do this in particular by looking at the science that I personally find the most interesting (this is my book, after all) and at the technologies which, in the decades and centuries to come, have the power to change the world for good or for ill more profoundly and more quickly than ever before.
Specifically, I want to describe the new science of genetics, and the technologies it produces, largely just to show how interesting it all is. Unless you find science interesting, you will not allow it to permeate your thinking. But there is no problem with this. Science is not a penance. It contains some of the greatest excitements that any pursuit has to offer: aesthetic as well as intellectual.
I also want to show what the new and astonishingly powerful technologies might achieve, both for good and not so good, and to suggest, however presumptuous it may seem, what the criteria should be for judging what is good.
Finally, in the last few chapters, I want to suggest ways in which we might begin to exercise sensible control, and at last begin to deploy technologies for proper ends. To be sure, I am not advocating that we should set up any particular bureaucracies, or make any particular changes of law. I want rather to address the kinds of attitudes of mind that are needed, and the kinds of problems that truly have to be addressed.
One way to write a book like this is to plunge straight in, with a list of agricultural or medical triumphs and disasters. But understanding is the important thing, and there can be no understanding without a feel for the underlying science. Besides, the science is the most interesting. So I will begin at the beginning. It is appropriate to start at the dawn of modern biology: in the middle of the nineteenth century, with Charles Darwin.
Heredity matters. It matters to each of us that our children, our parents, our families, are ours. It has mattered too much and too often in history that some of us belong to this family, or this race, and other people belong to another; so much, indeed, that human history (and probably much of prehistory) has been punctuated by genocide, which literally means the elimination of a people, but in practice tends to imply the elimination of people perceived to be different; at least, when the people attacked are not perceptibly different, as in civil war, the sin is commonly felt to be the greater. Heredity matters to animals as well; many have evolved ways of avoiding incest, at least between siblings (though father/daughter relationships are harder to avoid); and many spend their time or risk their lives in helping their offspring or their siblings, while treating non-relatives of their own species as rivals. Many plants avoid incest by chemical means; they can mate successfully only with others that are of the same species, and yet are subtly different from themselves.
Genetics is the study of heredity – or, more specifically, of the mechanisms of heredity. Because heredity matters, genetics matters. Indeed, of all the life sciences, genetics probably matters the most of all.
Genetics, then, lies at the heart of myths, of culture, and of the most basic instincts of people and other animals. Human concern with heredity is as old as humanity itself, older, indeed, for it also occupied all our animal ancestors. This book is an overview of the modern science of genetics. I will begin just before that science properly began: with Charles Darwin, and in particular with his pivotal publication of 1859, On the Origin of Species by Means of Natural Selection.
HEREDITY AND CHARLES DARWIN
John Maynard Smith once opined that if Charles Darwin had not written Origin of Species he would still be remembered ‘as the greatest of all field naturalists’.
On several counts, then, Darwin can reasonably be said to have been the greatest biologist of all time. He was certainly not the first to conceive the notion that living things evolved, one from another, and were not simply created in their contemporary form, but he was the first to provide a truly plausible mechanism whereby they could have changed in the way they have as the generations passed. The mechanism he proposed was that of natural selection.
Darwin’s hypothesis of evolution by means of natural selection has two main components. First, it borrows from the prognostications of the English cleric Thomas Malthus – who, at the turn of the eighteenth and nineteenth centuries argued that the human population was bound to outgrow its ability to produce more food, and so was bound, sooner or later, to run into severe trouble. Darwin applied this principle to all living things. All, he perceived – even slow breeders, like elephants – seemed bound to produce more offspring than their environment could support. So, like it or not, all creatures were bound to be thrown into competition with their fellows. Note indeed that in Darwin’s view the main competition was not between a wild horse and the wolf that eats it, but between two wild horses that are both trying to escape from the same wolf: when the race is to the swift.1 This has very interesting implications of many kinds as we will see in later chapters.
Second, Darwin perceived that in any one generation, individuals of the same species vary. One wild horse is very much the same as another wild horse of the same age and sex, but they are not identical. Some do run faster than others. The faster one is indeed the one who escapes.
These two components – inevitable competition, and variation – lead to what Darwin called ‘descent with modification’. If there were no variation, then there would have been no increase in the speed of horses as the generations passed – although such an increase can certainly be inferred from the fossil record. If all wild horses ran at identical speed, then it would be a pure lottery as to which one fell to the wolf. On the other hand, if there were no wolves (or lions or bears, or what you will) to chase the horses, then there would be no particular reason why swift ones should survive at the expense of slow ones. So the competition between horses does not simply lead to a decimation – a random removal of a few, in the way that Roman armies removed a few soldiers pour encourager les autres. It ensures that the ones that are best adapted to the circumstances – what Herbert Spencer, following Darwin, called the ‘fittest’ – are the ones that survive, and they, of course, are the most likely to produce offspring.
Note – which is why this is all so relevant – that Darwin’s notion of evolution, the crucial biological insight of the greatest of biologists, rests on two assumptions about the nature of heredity. First, it assumes that like begets like: swift horses are more likely to give birth to more swift horses, than slow horses are. If it were not so – if all horses gave birth to a random selection of more horses – then natural selection would not work, because the horses born in the next generation would turn out in the same way, whoever survived in the generation before. But then, this observation is hardly exceptionable: resemblances do run in families (and Darwin made friends with breeders of livestock and plants, and himself belonged to an enormous extended family).
Second, however, a system of heredity that could support the mechanism of natural selection would have to allow variation to occur. Again, this is a common observation. Siblings tend to resemble each other more than they resemble other people chosen at random, but siblings are never identical unless they are identical twins (and even they diverge through life’s vicissitudes).
Darwin was a very thorough thinker, and a tremendous worrier (none more so!). He provided the explanation he set out to provide: a plausible mechanism of evolution. But to be perfectly happy in his own mind (and indeed to satisfy all his critics, many of whom were extremely astute) he also wanted to provide a mechanism of heredity that could, in practice, underpin his mechanism of natural selection: one that would ensure that ‘like begets like’, but would also produce at least a modest degree of variation in each generation. In this, he failed. As he lamented in one doleful passage in Origin of Species:
… no one can say why the same peculiarity in different individuals … is sometimes inherited and sometimes not so; why the child often reverts in certain characters to its grandfather, or much more remote ancestor; why a peculiarity is often transmitted from one sex to both sexes, or to one sex alone, more commonly but not exclusively to the like sex.
Now, of course, the mechanisms of heredity have been worked out. As this chapter will soon explain, they are in principle very simple, so simple that some biologists have wondered at Darwin’s failure to work them out for himself. Some have even gone so far as to suggest that Darwin was, in fact, not particularly bright.
But those who doubt Darwin’s intelligence are themselves immensely foolish. It is not pure chauvinism that prompts me to defend Darwin as the greatest genius of biology. We could argue simply that none of Darwin’s immediate peers, who included people of unquestioned intellect – Thomas Huxley comes most obviously to mind – was able to infer a plausible mechanism of heredity either.
In fact, if we think about the matter objectively, Darwin’s ‘failure’ to provide a plausible mechanism of heredity is absolutely typical of the history of science in general. Only a small proportion of scientific cogitation leads to insight. The rest leads into blind alleys, and once the scientist is in a blind alley, it is extremely difficult for him or her to get out again. Usually, scientists are rescued from the various gum trees up which they climb only by their peers, who are looking at the problem from a different angle.
Darwin, I believe, was simply the wrong kind of thinker to arrive at the correct mechanism of heredity. He conceived his grand overview of evolution by looking at thousands of different instances, in thousands of different species: beetles, finches, barnacles, orchids, human beings; in other words, through the eyes of a tremendously accomplished naturalist. Nothing short of such a grand sweep could suggest a convincing mechanism that could be seen to apply to all of them.
But when you start to look at the details of heredity on such a grand scale, confusion reigns. As we will see – and as indeed is common experience – even very simple mechanisms of heredity can give rise to complex patterns of inheritance. Besides, there are mechanisms which, though simple in principle, are not particularly simple in detail, and they produce enormously complicated patterns of inheritance. Add to that the problem of sudden random change, sometimes caused by genetic mutation (just to anticipate) and sometimes caused by ‘recessive’ genes that make themselves felt only now and again, and sometimes caused by accidents or diseases in the womb (accidents which, in Darwin’s time, could not easily have been distinguished from true genetic changes). Any character that an individual is born with is, by definition, ‘congenital’, but congenital characters (such as congenital disorders) may result from particular genes, or may be caused by accidents in the womb or, for example, disease organisms passed on by the mother. Characters that are properly called ‘hereditary’ cannot be assumed to be genetic, either: for example, syphilis may be passed from generation to generation. In short, any line of inheritance occasionally throws up ‘sports’, or ‘monsters’, creatures that are quite out of the ordinary. All in all, it is quite impossible to see a coherent pattern of inheritance simply by scanning the whole of life, as a naturalist tends to do. Darwin’s cri de coeur in Origin is all too easy to explain.
However, if Darwin did have a true intellectual fault, it was that he was not numerate. He admired people who were, like his cousin, the pioneer statistician Francis Galton. He fully acknowledged the importance of maths in rigorous analysis. But his own experiments, though beautifully meticulous and inclusive, tended primarily to be qualitative: ‘This happens, and this and this’. Statistical analysis was lacking. As will become evident throughout this book, you cannot carry out serious genetic studies – indeed you hardly see the patterns of heredity at all – unless you are a statistician (although in practice there is no maths in this book, largely because the author is roughly as innumerate as Darwin). One important point is that statistical analysis depends on large samples; you simply cannot see the patterns in small samples (or if you do it is only by luck). If Darwin had had several hundred children instead of a mere ten or so, and several wives instead of one, and several thousand cousins instead of a few score, then he might well have been able to infer, for example, ‘why the same peculiarity … is sometimes inherited and sometimes not so’. But observations even of all the hundreds of people randomly encountered throughout his life could not truly reveal the orderly patterns.
In fact, Darwin did entertain two notions of heredity in particular: both germane to our theme. First, throughout his life he toyed with variations on the notions of the French biologist of the early nineteenth century, Jean-Baptiste Lamarck. Lamarck suggested that offspring inherit characteristics that were ‘acquired’ by their parents. Suppose, for example, that ancestral giraffes had short necks. Suppose that those ancestral giraffes spent their lives stretching those necks, to reach the higher leaves. As a result of all those efforts, said Lamarck, the offspring would be born with slightly longer necks than their parents. They too would stretch, and their offspring in turn would have even longer necks. And so on.
Such a mechanism was finally scotched in the late nineteenth century by the German biologist August Weismann. He suggested that information from the body cells (such as the muscle cells of a giraffe’s neck) did not pass to the gametes (the eggs and sperm), so that heredity could not directly be influenced by the activities of the parents. Even so, Lamarck’s hypothesis was far from foolish, and the derision he received in his own lifetime was founded in prejudice and ignorance. There should be no disgrace in science in being wrong, only in being dishonest, or dogmatic, or obfuscatory.
Besides, there is a twist to Lamarckism that makes it highly relevant today. After all, we may say – following Darwin’s theory of natural selection – that giraffes did not acquire long necks because their parents stretched their own necks; it was just that natural selection favoured the particular individual giraffes who happened (by chance) to have the longest necks.
Ah, we may ask, but why did natural selection favour long necks in giraffes? Why did it not favour long necks in okapis or anteaters? The answer is – because the ancestral giraffes were in fact feeding on leaves in high trees, and okapis and anteaters were not. In other words, the stretching of the ancestral giraffe necks did not lead directly to long-necked offspring. But it was only because the ancestral giraffes had a predilection for feeding in tall trees that natural selection favoured long necks in the first place. In other words, animals do have some (unconscious) ‘control’ over their own evolution, even though natural selection is the mechanism that finally applies. At least, they tend (albeit unconsciously) to put themselves in a position in which natural selection favours such-and-such a character, rather than another.
Darwin, however (just to hammer this point down), was not looking to Lamarck for an explanation of evolutionary change: natural selection is in general an alternative to Lamarck’s ‘inheritance of acquired characteristics’. He did, however, entertain the idea that the mechanism of inheritance that Lamarck proposed might be correct, and that it could underpin natural selection just as well as it underpinned Lamarck’s own theory of evolution. Indeed, after Darwin published Origin of Species, he wrote a long essay suggesting that body cells (such as giraffe neck cells) in fact produce ‘gemmules’ or ‘propagules’, which, he suggested, contained summaries of information about themselves; and that these summaries then passed to the reproductive organs, thence to become part of the hereditary information. He called this proposed mechanism, ‘pangenesis’. It was, of course, in direct opposition to the notions of Weismann, which were published a couple of decades later.
Darwin always sought the opinions of his friends, and he asked Thomas Huxley what he thought of pangenesis. Huxley put on his ‘sharpest spectacles and best thinking cap’ and replied with wonderful diplomacy: ‘Somebody rummaging among your papers half a century hence will find Pangenesis and say, “See this wonderful anticipation of our modern theories, and that stupid ass Huxley preventing his publishing them”.’2 But Huxley, as Darwin well knew, was a very wise ass indeed, and he kept his ingenious but crackpot notion to himself.
In general – whatever the details – Darwin supposed that parental characters were combined (more or less) in the offspring by a kind of blending, like a mixing of inks. He must have known that this was unsatisfactory. After all, red flowers crossed with white flowers may produce pink flowers (as we will see). But the cross may equally well produce offspring that are all red, or all white, or a mixture of the two.
There was a broader objection, however, one pointed out in 1867 by a professor of engineering from Glasgow University, Fleeming Jenkin. For Darwin, in Origin, was not seeking simply to explain evolutionary change. He affected – as the title of his seminal book proclaimed – to explain the origin of species. The central notion of the species (at least in Darwin’s day) was that each species differed qualitatively from another. The new species should be able to shake off the qualities of the ones that came before. But Jenkin – albeit with the racialism typical of his time – suggested a scenario that would seem to proscribe such radical change. Thus, he said, a white man cast away on an island of black people might well be acknowledged as their king. If he were, then he would enjoy all the reproductive success he might hope for. This reproductive success would be a measure of his ‘fitness’, in that particular environment; and hence the deified white man in the island of blacks would be bound to be favoured by natural selection, as envisaged by Darwin.
Yet, said Jenkin, this hypothetical successful white man ‘cannot blanch a nation of negroes’.3 In short, the ‘blending’ inheritance envisaged by Darwin could not apparently produce the kind of absolute changes that Darwin envisaged – changes that indeed could lead to the origin of new species.
In summary, Darwin produced the theory that has transformed biology, and indeed has changed the course of modern philosophy more profoundly than any other thinker of the past three centuries.4 Yet the mechanism he proposed cannot work unless the process of heredity operates in a particular way: a way that can produce variation from generation to generation even while respecting the general condition that ‘like begets like’; and in a way that would allow obsolete characters to be shuffled off completely and absolutely. But what that mechanism might be, Darwin failed absolutely to perceive.
Here we come to yet another irony, in fact to several more. First, the mechanism of inheritance that Darwin sought and needed was worked out and published during his own lifetime – indeed, just a few years after Origin appeared – by a scientist/monk in what was then called Moravia. Second, however, this crucial insight was overlooked by the scientific community at large, and was in fact forgotten until rediscovered at the beginning of the twentieth century. Third, when the vital mechanism of inheritance was finally rediscovered, it was not at first acknowledged as the key to Darwinism, the means by which natural selection could actually work. By contrast, biologists argued for several decades that if the newly discovered mechanism of inheritance was correct, then natural selection must be wrong.
But I am running ahead of the story. The monk who provided the vital mechanism that Darwin needed was Gregor Mendel.
GREGOR MENDEL
Gregor Mendel (1822–1884) was almost an exact contemporary of Darwin: he was born just thirteen years after Darwin was born, and died two years after Darwin died. By the mid-1860s he had completed experiments which provided precisely the mechanism that Darwin’s theory of evolution needed to round it off. Many commentators have said what a pity it was that Darwin never knew of Mendel’s work. But then, they sigh, Mendel was a monk, who did his work in the Augustinian monastery of St Thomas at Brunn in Moravia (now Brno in Slovakia) – a distant country of which we knew as little then as Neville Chamberlain apparently did in 1938. Mendel announced his pivotal ideas in two lectures in the Natural History Society of Brunn, and they were published in the society’s Transactions for 1866.
Yet Mendel was not a country bumpkin. He had studied mathematics, physics and biology in Vienna. Moravia and Brunn were not obscure. There was almost a century to go before the ‘Iron Curtain’ descended: Moravia in the mid-nineteenth century was very much a part of Europe. Sets of the essential Transactions were kept in England both in the Royal and the Linnean Societies. Darwin was extremely widely read, and other biologists brought matters of interest to his attention. Mendel also visited England, and some have rumoured that he actually visited Darwin. The great British population geneticist E.B. Ford avers that he did not: as Ford records in Understanding Genetics (Faber and Faber, London, 1979, p. 13) ‘I am … the last of those who shared their friends with Darwin, and among the last who knew one of his children (Major Leonard) quite well … and am confident that no meeting between Darwin and Mendel ever took place’. Yet I remain intrigued by the notion that Darwin may well have known of Mendel’s key experiments but – like everyone else at the time – failed to see their significance.
Such a failure does not reflect ill on Darwin. It would be perfectly understandable. After all, Mendel conducted his experiments with a few carefully selected characters in carefully selected plants – that is to say, with garden peas – under highly contrived conditions. Not even he was able to see that he had in fact discovered universal laws. It would indeed have been stretching credibility too far to suggest that the rules he had worked out in peas could also explain the caprices of inheritance in human beings. Here we have the nub of the problem, for although the basic rules of inheritance are simple, and universal, the realities of inheritance are such that the existence of those rules could not be inferred except by exploring deliberately simplified cases, in highly contrived circumstances. But Darwin was a broad thinker, and in this, he was hoist on the petard of his own breadth.
Mendel carried out his seminal experiments on the garden pea, Pisum sativum. In particular, he explored the patterns of inheritance of eight different characters, which included stature (short or tall), the colour of the unripe pod (yellow or green), the colour of the cotyledons within the seed (yellow or green), and the behaviour of the seed as it dried – whether it remained round, or became wrinkled.
Clearly, his experiments were highly contrived. He knew perfectly well – because he was an accomplished horticulturalist, as indeed were his parents – that the pattern of inheritance in domestic plants is sometimes orderly, and sometimes much less so. Garden peas are inbreeders: the seeds are fertilised by pollen from the same plant. Indeed the pollen comes from the same flower: it has to, because the stigma which receives the pollen and the anthers that produce it are completely enveloped by the petals. Inbreeding plants are also true-breeding: you do not see the erratic pattern of inheritance that Darwin observed in human beings (and other animals) and which can also be seen (for reasons that will become evident later) in, say, cabbages. Mendel knew, before he began, that peas would give him clear results, if any plant would; and that cabbages (say), would probably not.
Furthermore, Mendel knew perfectly well that only some characters in garden peas are inherited in an orderly pattern. Indeed he recorded the fact:
The various forms of peas selected for crosses showed differences in length and colour of stem; in size and shape of leaves; in position, colour, and size of flowers; in length of flower stalks; in colour, shape, and size of pods; in shape and size of seeds; and in colouration of seed coats and albumen. However, some of the traits listed do not permit a definite and sharp separation, since the difference rests on a ‘more or less’ which is often difficult to define. Such traits were not usable for individual experiments; these had to be limited to characteristics which stand out clearly and decisively in plants.
So Mendel very deliberately elected to study the inheritance of a few carefully selected traits, in a well-chosen species. This is good science; it is a well-established principle that complex issues are often best approached through the study of simple cases. We can see, though, why even those who we know were aware of Mendel’s work – why even Mendel himself – did not perceive that the rules that applied to highly selected characters in highly selected plants in practice apply to most characters in most animals, plants and fungi.
Yet Mendel’s experiments, deliberately contrived to give simple results, also showed why it was so difficult to discern any order in inheritance among creatures at large, for even the simple examples he chose to study led quickly to enormous complexities.
Thus, to begin as simply as possible, round-seeded varieties of garden peas when left to self-pollinate produced round-seeded offspring, and wrinkle-seeded varieties, when self-pollinating, produced wrinkle-seeded offspring. This is what ‘true-breeding’ implies. But in one of his first experiments, Mendel explored what happened when round-seeded were crossed with wrinkle-seeded. This he did by removing the anthers of one kind, so they could not self-pollinate, and then brushing their stigmas with the pollen of the other kind; the time-honoured technique of the plant breeder.
A cross between two varieties is called a hybrid. The first generation following a cross between any two specified parents (whether of the same or different varieties) is called the F1 generation; and their offspring are in turn called the F2 generation, and so on. In the event, the answer to the first of Mendel’s questions is that the F1 hybrid offspring of round-seeded and wrinkle-seeded peas all had round seeds.
What then had happened to the quality of wrinkledness? Mendel now allowed the F1 hybrid plants to self-pollinate. The result of this was that some of the F2 generation had round seeds – but in others, the quality of wrinkledness had mysteriously reappeared. This, of course, is exactly the kind of phenomenon that Charles Darwin had drawn attention to: that a character may miss a generation, and then crop up in a later one.
Mendel was not content merely to observe that some F2 plants were round and some were wrinkled. He counted them. There were 5474 round ones, and 1850 wrinkled ones. The ratio is very nearly three to one.
A short diversion is called for. The great British twentieth-century statistician R.A. Fisher pointed out that Mendel’s figures were, in fact, too good to be true. All Mendel’s published results show very clearly the kinds of ratios that confirm his ideas. But life isn’t like that. In truth, all biological systems are subject to time and chance, and the kinds of figures that are really obtained from experiments such as Mendel’s only rarely show exactly what they are supposed to show. Some critics have darkly hinted that Mendel, holy man though he was, fiddled his results.
I do not believe for one second that that is the case. Here, rather, is yet another quirk of science history. For it is only in the twentieth century that biologists (like physicists) have routinely begun to work in teams, and it is only now that those teams have come routinely to include statisticians. Indeed, everyone acknowledges nowadays that if complex experiments in biology are truly to be informative then statisticians must be involved at the design stage.
Mendel was not a statistician in the modern sense – for indeed, statistics in his day was still primitive. His statistics was of the commonsense, accountant’s variety. He probably did not perceive that rigorous statistics were necessary to test hypotheses. Probably, rather, he saw the experimental results primarily as a means of illustration, of confirming what common sense already showed was obvious. In the same way, two centuries earlier, Isaac Newton recorded precise experiments with light that he could not possibly have carried out. But Newton, unimpeachably honest, was not at all contrite. ‘Of course the experiment did not turn out exactly as I recorded,’ he replied when challenged (though I paraphrase): ‘This is the seventeenth century for Goodness’ sake! What do you expect with prisms like these? But it is obvious what would have happened, if I had been able to control all the factors precisely.’ Mendel doubtless felt the same. He counted peas until (so common sense suggested) he had counted enough to make the point. So what else do you need?
The three-to-one ratio that Mendel observed has several implications. First, it suggests that inheritance can indeed follow simple arithmetical rules. The patterns of inheritance are not invariably messy. Second, the clear ratio clearly militates against the kind of explanation of inheritance that Darwin found himself adhering to: that inheritance is like a mixing of inks. There was no mixing here. The F2 peas were either wrinkled, or they were not. They were not half-wrinkled, or wrinkled in parts. The quality of wrinkledness had not been diluted, and still less had it been extinguished. It had merely been suppressed for a generation. But how?
Mendel, genius that he unquestionably was, provided an explanation that was simple, satisfying and – so all experiments subsequently suggest – correct. The characteristics of a plant (‘characters’) were determined not by vague pervasive philtres that could be mixed like inks. Instead, each character was determined by a discrete ‘factor’ (Mendel used the German Anlagen for ‘factors’). These are the factors that we now call genes, and for convenience, I will use that excellent term from now on.
Each individual, said Mendel, contains two copies of each gene; one inherited from its mother, and one from its father. And each individual (just to round off the point) passes only one copy of each gene on to its offspring. And this is the essence of classical genetics, from which all else follows. The rest of this book is a footnote. It is, however, quite an interesting footnote, so I will continue.
Each true-breeding round pea, so Mendel inferred, contained two copies of the gene for roundness, and each true-breeding wrinkled pea contained two copies of the gene for wrinkledness. In fact, of course, the roundness gene and the wrinkledness gene are different versions of the same gene; that is, different versions of the gene that determines seed shape. Different versions of the same gene are called alleles of that gene, and ‘allele’ is an extremely important term.
Each kind of pea passes on only one copy of its pea-shape gene to its offspring. Hence the true-breeding round pea passes on one roundness allele to each offspring, and the true-breeding wrinkled pea passes on one wrinkledness allele to each offspring. They can do nothing else, each one contains only one kind of allele for that particular gene. Hence the F1 offspring of a cross between a true-breeding round and a true-breeding wrinkled all contain one roundness allele and one wrinkledness allele.
Mendel realised the roundness allele is dominant over the wrinkledness allele. So long as it is present, the wrinkledness allele remains inoperative. That is, it is recessive. So the peas of the F1 cross-bred generation are all round, because in each one, only the roundness gene makes itself felt.
Consider what happens now, however, when the F1 offspring themselves start to breed. Stage one is to produce gametes: eggs or sperm. Each gamete can contain only and copy of each kind of gene. But the F1 offspring each contain two versions of each pea-shape gene; both a wrinkledness allele and a roundness allele. Each one can pass on only one of the two alleles to each gamete: either the wrinkledness allele or the roundness allele but not both.
Hence, if these F1 offspring are randomly crossed with other F1 offspring the subsequent, F2 generation contains a fine old mixture. Each individual could, in principle, inherit two roundness alleles (one from each parent) – in which case its own seeds would be round. Or it could inherit two wrinkledness alleles – and then its seeds would be wrinkled. Or it could inherit one roundness and one wrinkledness allele – in which case, because roundness is dominant, its seeds would be round, just as if it had inherited two roundness alleles. Common sense immediately allows us to see that there are three ways out of four in which the F2 seeds could finish up being round, and only one way out of four in which they could finish up being wrinkled. If common sense fails, Figure 1.1 makes it all obvious at a glance. In fact, as Mendel found, in this experiment the ratio of round peas to wrinkled peas in the F2 generation is indeed 3:1.