The Ascent of Man

by Jacob Bronowski

  We do the experiment exactly throughout as Mendel did. We start by making a hybrid of tall and short, choosing the parent plants as Mendel specified:

  In experiments with this character, in order to be able to discriminate with certainty, the long axis of six to seven feet was always crossed with the short one of ¾ of a foot to 1½ feet.

  In order to make sure that the short plant does not fertilise itself, we emasculate it. And then we artificially inseminate it from the tall plant.

  The process of fertilisation takes its course. The pollen tubes grow down the ovules. The pollen nuclei (the equivalent of sperm in an animal) go down the pollen tubes and reach the ovules just as they do in any other fertilised pea. The plant bears pods that do not yet, of course, reveal their character.

  The peas from the pods are now planted. Their development is at first indistinguishable from that of any other garden peas. But though they are only the first generation of hybrid offspring, their appearance when fully grown will already be a test of the traditional view of inheritance held by botanists then and long afterwards. The traditional view was that the characters of hybrids fall between the characters of their parents. Mendel’s view was radically different, and he had even guessed a theory to explain it.

  Mendel had guessed that a simple character is regulated by two particles (we now call them genes). Each parent contributes one of the two particles. If the two particles or genes are different, one will be dominant and the other recessive. The crossing of tall peas with short is a first step in seeing if this is true. And lo and behold, the first generation of hybrids, when fully grown, are all tall. In the language of modern genetics, the character tall is dominant over the character short. It is not true that the hybrids average the height of their parents; they are all tall plants.

  Now the second step: we form the second generation as Mendel did. We fertilise the hybrids, this time with their own pollen. We allow the pods to form, plant the seeds, and here is the second generation. It is not all of anything, for it is not uniform; there is a majority of tall plants, but a significant minority of short plants. The fraction of the total that consists of short plants should be calculable from Mendel’s guess about heredity; for if he was right, each hybrid in the first generation carried one dominant and one recessive gene. Therefore in one mating out of every four between first generation hybrids, two recessive genes have come together, and as a result one plant out of every four should be short. And so it is: in the second generation, one plant out of four is short, and three are tall. This is the famous ratio of one out of four, or one to three, that everyone associates with Mendel’s name – and rightly so. As Mendel reported,

  Out of 1064 plants, in 787 cases the stem was long, and in 277 short. Hence a mutual ratio of 2.84 to 1 … If now the results of the whole of the experiments be brought together, there is found, as between the number of forms with the dominant and recessive characters, an average ratio of 2.98 to 1, or 3 to 1.

  It is now clear that the hybrids form seeds having one or other of two differentiating characters, and of these one half develop again the hybrid form, while the other half yield plants which remain constant and receive the dominant or the recessive characters [respectively] in equal numbers.

  Mendel published his results in 1866 in the Journal of the Brno Natural History Society, and achieved instant oblivion. No one cared. No one understood his work. Even when he wrote to a distinguished, rather stuffy figure in the field, Karl Nägeli, it was clear that he had no notion what Mendel was talking about. Of course, if Mendel had been a professional scientist, he would now have pushed to get the results known, and at least published the paper more widely in France or Britain in a journal that botanists and biologists read. He did try to reach scientists abroad by sending them reprints of his paper, but that is a long shot for an unknown writing in an unknown journal. However, at this moment, in 1868, two years after the paper was published, a most unexpected thing happened to Mendel. He was elected abbot of his monastery. And for the rest of his life he carried out his duties with commendable zeal, and a touch of neurotic punctilio.

  He told Nägeli that he hoped to go on doing breeding experiments. But the only thing that Mendel now was able to breed were bees – he had always been anxious to push his work from plants to animals. And of course, being Mendel, he had his usual mixture of splendid intellectual fortune and practical bad luck. He made a hybrid strain of bees which gave excellent honey; but alas, they were so ferocious that they stung everybody for miles around and had to be destroyed.

  Mendel seems to have been more exercised about tax demands on the monastery than about its religious leadership. And there is a hint that he was regarded as unreliable by the Emperor’s Secret Police. Under the abbot’s brow there lay a weight of private thought.

  The puzzle of Mendel’s personality is an intellectual one. No one could have conceived those experiments unless they had clearly in their minds the answer that they were going to get. It is a strange state of affairs, and I should give you chapter and verse for that.

  First, a practical point. Mendel chose seven differences between peas to test for at the time, such as tall versus short, and so on. And indeed the pea does have seven pairs of chromosomes, so you can test for seven different characters in genes lying on seven different chromosomes. But that is the largest number you could have chosen. You could not test for eight different characters without getting two of the genes lying on the same chromosome, and therefore being at least partially linked. Nobody had thought of genes or heard of linkage then. Nobody had even heard of chromosomes at the time when Mendel was actually working on the paper.

  Now surely you can be destined to be the abbot of a monastery, you can be chosen by God, but you cannot have that luck. Mendel must have done a good deal of observation and experiment before the formal work, in order to tease out these and convince himself that seven qualities or characters was just what he could get away with. There we glimpse the great iceberg of the mind in that secret, hidden face of Mendel’s on which the paper and the achievement float. And you see it; you see it on every page of the manuscript – the algebraic symbolism, the statistics, the clarity of the exposition; everything is modern genetics, essentially as it is done now, but done more than a hundred years ago by an unknown.

  And done by an unknown who had one crucial inspiration: that characters separate in an all-or-none fashion. Mendel conceived that in an age when biologists took it as axiomatic that crossing produces something between the two characters of the parents. We can hardly suppose that a recessive character never appeared, and we can only speculate that every time breeders observed this in a hybrid, it was thrown away because they were convinced that heredity must go by averaging.

  Where did Mendel get the model of an all-or-nothing heredity? I think I know, but of course I cannot look into his head either. But there does exist one model (and it has existed since time immemorial) which is so obvious that perhaps no scientist would think of it: but a child, or a monk, might. That model is sex. Animals have been copulating for millions of years, and males and females of the same species do not produce sexual monsters or hermaphrodites: they produce either a male or a female. Men and women have been going to bed for upwards of a million years, at least; and they produce – what? Either men, or women. Some such simple, powerful model of an all-or-nothing way of passing on differences must have been in Mendel’s mind, so that the experiments and the thought were clearly made for him of whole cloth, and fitted from the inception.

  The monks, I think, knew this. I think they did not like what Mendel was doing. I think the bishop, who demurred at the peabreeding experiments, did not like it. They did not like his interest in the new biology at all – in Darwin’s work, for example, which Mendel read and was impressed by. Of course, the routabout revolutionary Czech colleagues whom he often sheltered in the monastery were fond of him to the end. When he died in 1884, barely at the age of sixty-two, the great Czech composer Le
oš Janáček played the organ at his funeral. But the monks elected a new abbot, and he burned all Mendel’s papers at the monastery.

  Mendel’s great experiment remained forgotten for over thirty years until it was resurrected (by several scientists independently) in 1900. So his discoveries belong in effect to this century, when the study of genetics all at once blossoms from them.

  To begin at the beginning. Life on earth has been going on for three thousand million years or more. For two-thirds of that time organisms reproduced themselves by cell division. Division produces identical offspring as a rule, and new forms appear only rarely, by mutation. For all that time, therefore, evolution was very slow. The first organisms to reproduce sexually were, it now seems, related to the green algae. That was less than a thousand million years ago. Sexual reproduction begins there, first in plants, then in animals. Since then its success has made it the biological norm, so that, for instance, we define two species as different if their members cannot breed with one another.

  Sex produces diversity, and diversity is the propeller of evolution. The acceleration in evolution is responsible for the existence now of the dazzling variety of shape, colour, and behaviour in species. And we must count it also responsible for the proliferation of individual differences within species. All that was made possible by the emergence of two sexes. Indeed, the spread of sex through the biological world is itself a proof that species become fitted to a new environment by selection. For sex would not be necessary if the members of a species could inherit the acquired changes by which individuals adapt themselves. Lamarck at the end of the eighteenth century proposed that naive and, as it were, solitary mode of inheritance; but if it existed, it could be passed on better by cell division.

  Two is the magic number. That is why sexual selection and courtship are so highly evolved in different species, in forms as spectacular as the peacock. It is why sexual behaviour is geared so precisely to the animal’s environment. If the grunion could have adapted themselves without natural selection, then they would not trouble to dance on the Californian beaches in order to match incubation to the period of the moon. For them and for all the mavericks of adaptation, sex would not be necessary. And sex is itself a mode of natural selection of the fittest. Stags do not fight to kill, only to establish their right to choose the female. The multiplicity of shape, colour, and behaviour in individuals and in species is produced by the coupling of genes, as Mendel guessed. As a matter of mechanics, the genes are strung out along the chromosomes, which become visible only when the cell is dividing. But the question is not how the genes are arranged; the modern question is, How do they act? The genes are made of nucleic acids. That is where the action is.

  How the message of inheritance is passed from one generation to the next was discovered in 1953, and it is the adventure story of science in the twentieth century. I suppose the moment of drama is the autumn of 1951, when a young man in his twenties, James Watson, arrives in Cambridge and teams up with a man of thirty-five, Francis Crick, to decipher the structure of deoxyribonucleic acid, DNA for short. DNA is a nucleic acid, that is, an acid in the central part of cells, and it had become clear in the preceding ten years that nucleic acids carry the chemical messages of inheritance from generation to generation. Two questions then faced the searchers in Cambridge, and in laboratories as far afield as California. What is the chemistry? And what is the architecture?

  The genes are strung out along the chromosomes which become visible when the cell is dividing.

  Large chromosomes of onion-skin cells.

  What is the chemistry? Which means, What are the parts that compose DNA and that can be shuffled about to make different forms of it? That was known pretty well. It was clear that DNA is made of sugars and phosphates (they were sure to be there, for structural reasons), and four specific small molecules or bases. Two of them are very small molecules, thymine and cytosine, in each of which atoms of carbon, nitrogen, oxygen, and hydrogen are arranged in a hexagon. And two of them are rather larger, guanine and adenine, in each of which the atoms are arranged in a hexagon and a pentagon joined together. It is usual in structural work to represent each of the small bases simply by a hexagon, and the large by the bigger figure, to draw attention to the shapes rather than the individual atoms.

  And what is the architecture? Which means, What is the arrangement of the bases that gives DNA the ability to express many different genetic messages? For a building is not a heap of stones, and the DNA molecule is not a heap of bases. What gives it its structure and therefore its function? It was clear by then that the DNA molecule is a long extended chain, but rather rigid – a kind of organic crystal. And it seemed likely that it would be a helix (or spiral). How many helixes in parallel? One, two, three, four? There was a division of opinion into two main camps: the two-helix camp and the three-helix camp. And then, at the end of 1952, the great genius of structural chemistry, Linus Pauling, in California proposed a three-helix model. The backbone of sugar and phosphate ran down the middle, and the bases stuck out in all directions. Pauling’s paper arrived in Cambridge in February 1953, and it was apparent to Crick and Watson that there was something wrong with it from the outset.

  It may have been mere relief, it may have been a touch of malicious perversity, which made Jim Watson decide there and then that he would go for the double helix. After a visit to London,

  by the time I had cycled back to college and climbed over the back gate, I had decided to build two-chain models. Francis would have to agree. Even though he was a physicist, he knew that important biological objects come in pairs.

  Moreover, he and Crick began to look for a structure with the backbones running on the outside: a sort of spiral staircase, with the sugars and phosphates holding it like two handrails. There were agonies of experimentation with cut-out shapes to see how the bases would fit as the steps in that model. And then, after one particularly wild mistake, all at once it became self-evident.

  I looked up, saw that it was not Francis, and began shifting the bases in and out of various other pairing possibilities. Suddenly I became aware that an adenine-thymine pair held together by two hydrogen bonds was identical in shape to a guanine-cytosine pair.

  Of course: on each step there must be a small base and a large base. But not any large base. Thymine must be matched by adenine, and if you have cytosine then it must be matched by guanine. The bases go together in pairs of which each determines the other.

  So the model of the DNA molecule is a spiral staircase. It is a right-handed spiral in which each tread is of the same size, at the same distance from the next, and turns at the same rate – thirty-six degrees between successive treads. And if cytosine is at one end of a tread, then guanine is at the other; and so for the other base pair. That implies that each half of the spiral carries the complete message, so that in a sense the other is redundant.

  Let us build the molecule on a computer. Schematically, that is a base-pair; the dotted lines between the ends are the hydrogen bonds that hold the two bases together. We will put it into the end-on position in which we are going to stack it. And now we will stack it at the bottom of the left-hand side of the computer picture, where we are going to build the whole molecule of DNA, literally step by step.

  Here is a second pair; it might be of the same kind as the first, or of the opposite kind; and it might face either way. We stack it over the first pair and turn it through thirty-six degrees. Here is a third pair, to which we do the same thing. And so on.

  These treads are a code which will tell the cell step by step how to make the proteins necessary to life. The gene is forming visibly in front of our eyes, and the handrails of sugars and phosphates hold the spiral staircase rigid on each side. The spiral DNA molecule is a gene, a gene in action, and the treads are the steps by which it acts.

  On 2 April 1953 James Watson and Francis Crick sent to Nature the paper which describes this structure in DNA on which they had worked for only eighteen months. In the w
ords of Jacques Monod, of the Pasteur Institute in Paris and the Salk Institute in California,

  The fundamental biological invariant is DNA. That is why Mendel’s defining of the gene as the unvarying bearer of hereditary traits, its chemical identification by Avery (confirmed by Hershey), and the elucidation by Watson and Crick of the structural basis of its replicative invariance, without any doubt constitute the most important discoveries ever made in biology. To which of course must be added the theory of natural selection, whose certainty and full significance were established only by those later discoveries.

  The model of DNA patently lends itself to the process of replication which is fundamental to life even before sex. When a cell divides, the two spirals separate. Each base fixes opposite to it the other member of the pair to which it belongs. This is the point of the redundancy in the double helix: because each half carries the whole message or instruction, when a cell divides the same gene is reproduced. The magic number two here is the means by which a cell passes on its genetic identity when it divides.

  The DNA spiral is not a monument. It is an instruction, a living mobile to tell the cell how to carry out the processes of life step by step. Life follows a time-table, and the treads of the DNA spiral encode and signal the sequence in which the time-table must go. The machinery of the cell reads off the treads in order, one after another. A sequence of three treads acts as a signal to the cell to make one amino acid. As the amino acids are formed in order, they line up and assemble in the cell as proteins. And the proteins are the agents and building blocks of life in the cell.

  Every cell in the body carries the complete potential to make the whole animal, except only the sperm and egg cells. The sperm and the egg are incomplete, and essentially they are half cells: they carry half the total number of genes. Then when the egg is fertilised by the sperm, the genes from each come together in pairs as Mendel foresaw, and the total of instructions is assembled again. The fertilised egg is then a complete cell, and it is the model of every cell in the body. For every cell is formed by division of the fertilised egg, and is therefore identical with it in its genetic make-up. Like a chick embryo, the animal has the legacy of the fertilised egg all through life.