Читать книгу Nature via Nurture: Genes, experience and what makes us human - Matt Ridley, Matt Ridley - Страница 9

The argument about human exceptionalism, swaying between Darwinian similarity and Cartesian difference, shows no sign of ending. Each generation is doomed to fight the same old battles. If you arrive in the world in a time when people have strayed a bit far into anthropomorphic similarity, then you can find a fresh argument for how different animals and people are. If the air is full of difference, then you can champion the similarities. Philosophy is like this: eternally unsettled and only occasionally disturbed by new facts.

Then came an unexpected threat to this pleasant debate. A threat of a resolution. A threat of defining once and for all, at root, what the difference is between a person and a chimpanzee; what you would have to do to a chimpanzee to make it into a person.

It happened about the same time that Jane Goodall was undermining the exceptionalism of human behaviour. Almost completely forgotten until rediscovered in the 1960s was an extraordinary experiment done by a Californian named George Nuttall in 1901 while at Cambridge University. He noticed that the more closely related two species were, the more their blood produced the same immune reaction in a rabbit. He injected blood from, say, a monkey into a rabbit repeatedly for some weeks, then a few days after the last injection extracted serum from the rabbit’s blood. That serum, mixed with the blood of a monkey, caused it to thicken as the immune reaction set in. Mixed with the blood of a different animal, it thickened more according to how closely related the species were. By this means Nuttall established that human beings were more closely related to apes than they were to monkeys. This ought to have been obvious from the lack of a tail and other features, but it was still controversial at the time.

In 1967 at Berkeley, Vincent Sarich and Allan Wilson revived Nuttall’s biochemical techniques in a more sophisticated form and used them to construct a ‘molecular clock’ that measured the actual length of time since two species had shared a common ancestor. They concluded that human beings had shared a common ancestor with the great apes not 16 million years ago, as was then conventional wisdom, but only about five million years ago. Anthropologists, whose fossils implied a more ancient split, reacted with contempt. Sarich and Wilson stuck to their guns. In 1975, Wilson asked his student Marie-Claire King to repeat the exercise for DNA in order to find the genetic differences between human beings and apes. She came back disappointed. It was impossible to find differences, she said, because human and chimpanzee DNA was so astonishingly similar: close to 99 per cent of the DNA in a human being was identical to that in a chimpanzee. Wilson was thrilled: the similarity was more exciting than the difference.

That figure has meandered a little since the 1970s. Most estimates place it at 98.5 per cent, although two recent detailed studies of actual stretches of genome came to a figure of 98.76 per cent.²⁶ However, just as the 98.5 per cent was seeping into the public consciousness, Roy Britten wrote a dramatic paper in 2002 showing that it was out by a mile. He confirmed that if you count only substitutions – i.e., letters in the text that are different between human and chimpanzee genes—you do indeed get a figure of 98.6 per cent. But if you then add in the textual insertions or deletions, the figure drops to 95 per cent.²⁷

Whatever. It was still a terrible shock to science to discover just how small was the genetic distance between the two species. ‘The molecular similarity between chimpanzees and humans is extraordinary because they differ far more than many other [closely related] species in anatomy and way of life,’ wrote King and Wilson.²⁸ An even greater shock was in store in 1984, when Charles Sibley and Jon Ahlquist at Yale found that chimpanzee DNA was more like human DNA than it was like gorilla DNA.²⁹ This was a moment of human dethronement similar to Copernicus placing the Earth within the solar system as just another planet. Sibley and Ahlquist placed the human species within the ape family as just another ape. From having our own distinct ape lineage stretching back 16 million years, we were now forced to admit that not only did we share a common ancestor not much more than five million years ago, but that we were the most recent branch of the family. Our common ancestor with the chimp lived after the common ancestor of both with the gorilla and long after the common ancestor of all three with the organg-utan. Incredible as it may seem, chimpanzees are more closely related to human beings than they are to gorillas (a conclusion that Britten’s reanalysis of the precise number does not alter). Nothing in the anatomy or fossil record of the African apes suggested such a possibility. Human beings are not the odd ones out.

Time has dulled these shocks. But there are more coming. Reading the DNA of a human being, alongside that of a chimpanzee, might once and for all define the difference between them. At the time of writing, the complete genome of the chimpanzee is not yet available. Even when it is, it may prove tricky to work out which differences are the ones that matter. The human genome contains about three billion ‘letters’ of code. Strictly speaking, these are chemical bases on a molecule of DNA, but since it is their order, not their individual properties, that determines what they produce, they can be treated as digital information. The difference between two individual human beings amounts, on average, to 0.1 per cent, so there are three million different letters between me and my neighbour. The difference between a human being and a chimpanzee is about 15 times as great, or 1.5 per cent. That equates to 45 million different letters. That is about ten times as many letters as there are in the whole Bible, or 75 books the length of this one. The book of digital differences between our two species, unannotated, would fill eleven feet of bookshelf. (The bookshelf of similarities, by contrast, would stretch to 250 yards.)

Look at it another way. Scientists now reckon that there are about 30,000 human genes. That is, scattered throughout the genome are 30,000 distinct stretches of digital information that are directly translated into protein machinery to run and build the body: a gene being a recipe for a protein. Chimpanzees almost certainly have roughly the same number of genes. Since 1.5 per cent of 30,000 is 450, then it seems to follow that we have 450 different, uniquely human genes. Not such a big number. The other 29,550 genes are identical in us and chimps. But this is actually most unlikely. It could instead be that every single human gene is different from every single chimp gene, but only 1.5 per cent of its text is different. The truth is bound to lie somewhere between the two. Many genes will be identical in closely related species; many will be slightly different. A very few will be utterly different.

The most visible difference is that all apes have one more pair of chromosomes than people do. The reason is simple enough to find: at some point in the past, two middle-sized ape chromosomes fused together in the ancestors of all human beings to form the large human chromosome known as chromosome 2. This is a surprising rearrangement, and it almost certainly means that chimp-human hybrids would be sterile if they could survive at all. It may have helped create what evolutionists delicately call ‘reproductive isolation’ between the species in the past.

But the rearrangement of the chromosomes does not necessarily imply a difference in genetic text at that spot. Although the chimpanzee genome is still largely terra incognita, already there are significant textual differences known between human and chimp (or other ape) genes. For example, whereas people have a mixture of A, B and O blood groups, chimpanzees have only A and O, while gorillas have only B. Likewise, there are three common variants of a human gene called APOE, and chimpanzees only have one – the one most associated with Alzheimer’s disease in people. There seems to be a distinct difference in the way thyroid hormones work in people compared with other apes. The significance of this is unknown. And a family of genes on chromosome 16 has undergone several bursts of duplication in the apes after they had separated from the monkey lineage 25 million years ago. Each set of these so-called ‘morpheus’ genes in human beings has diverged rapidly in sequence from each other and from those in other apes – evolving at nearly 20 times the normal rate. Some of these morpheus genes might indeed be described as uniquely human genes. But exactly what these genes do, or why they are evolving apart so rapidly in apes, remains mysterious.³⁰

Most of these differences are also variable among people; there is nothing here unique to human beings as a whole. In the mid-1990s, however, the first genetically unique feature universal to all people and absent from all apes was discovered. Several years before, a medical professor in San Diego named Ajit Varki became intrigued by a unique form of human allergy: an allergy to a particular kind of sugar (a certain ‘sialic acid’) found attached to proteins in animal serum. This immune reaction is partly responsible for the severe reaction that people often have to horse serum used as a snake-bite antidote, for example. We human beings simply cannot tolerate this ‘Gc’ version of sialic acid, because we do not have it in the human body. Varki, together with Elaine Muchmore, soon discovered the cause by first noting that unlike human beings, chimpanzees and other great apes did have Gc. The human body does not manufacture Gc sialic acid because it lacks the enzyme for making it from Ac sialic acid. Without the enzyme, human beings cannot add an oxygen atom to the Ac form. All human beings lack the enzyme, but all apes have it. This was the first universally true biochemical difference between us and them. Fittingly, at the end of a millennium that saw us humiliatingly demoted from the centre of the universe and the apple of God’s eye to just another ape, Varki now seemed to suggest that we differ by just a single atom on a humble sugar molecule: and an omission at that! Not a promising locus for the soul.

By 1998 Varki knew why we were peculiar: a 92-letter sequence was missing from a gene called CMAH on chromosome 6 in human beings, a gene that codes for the enzyme that makes Gc. Next he discovered how it had gone missing. Right in the middle of the gene was an Alu sequence, a sort of ‘jumping gene’ of a kind that infests our genome. In the ape genome there is a different and more ancient Alu, but the one in the human gene was of a sequence known to be unique to human beings.³¹ So some time after the divergence of the human and chimp lineage, this Alu had done what it does best, which is to jump into the CMAH gene, swap places with the older Alu and accidentally remove the 92-letter chunk of the gene while it was about it. (If this all sounds like double genetic Dutch, try thinking of it this way: a computer virus has destroyed one of your files.)

Varki’s discovery initially raised a big yawn from the scientific establishment. So what, they cried, you have found a gene that is bust in human beings but not in apes. Big deal. Varki is not easily discouraged, and by now he was interested by the whole subject of human-ape difference. The first issue was to pinpoint when the mutation had occurred. DNA cannot be recovered from ancient fossils of human ancestors, but sialic acid can be. He found that Neanderthals were like us, in having Ac, but no Gc, but older fossils (from Java and Kenya) were all from warmer climates and their sialic acids had degraded too far. However, by counting the number of changes in the defunct human CMAH gene, and using a molecular clock, his colleague Yuki Takahata has been able to estimate that the change happened about 2.5 or 3 million years ago in some human being who is now one of the ancestors of all people alive.

Varki began to investigate other possible consequences of the mutation. Most other animals seemed to have the working gene, even sea urchins, but if the gene is ‘knocked out’ in the embryo of a mouse, the mouse grows up healthy and fertile. Sialic acid is a sugar found on the outside of cells, like a sort of flower growing from the cell surface. It is one of the first targets for infectious pathogens including botulism, malaria, influenza and cholera. Lacking one of the common forms of sialic acid might make us more or less vulnerable to these diseases than our ape relatives (cell-surface sugars seem to be a sort of first line of defence in the immune system). But the most intriguing thing about the Gc form of sialic acid is that it is easily found throughout the body of mammals except in the brain. Varki’s gene is almost entirely switched off in the brains of mammals. There must be some reason why you cannot operate a mammalian brain properly unless you switch this gene off almost completely. Perhaps, muses Varki’s, the expansion of the human brain, which accelerated about two million years ago, was made possible by going one further and switching the gene off altogether throughout the body. He admits it is a ‘wild idea’ for which he has no evidence; he is in uncharted territory. Intriguingly, he has since found another gene concerned with processing sialic acid that is also knocked out in human beings.³²

Even esoteric research like this may have practical consequences. It gives a strong reason to abandon the idea of xeno-transplantation, the transplanting of animal organs into people: allergic reactions to the Gc sugars in animal organs are almost inevitable. Since you can find traces of Gc sialic acid in human tissues, presumably from animal food, Varki has been drinking diluted Gc sialic acid recently to test how his own body handles it. He wonders if some of the diseases that are caused by eating ‘red meat’ may be associated with encountering this animal version of the sugar. But Varki is the first to admit that the vast range of differences between human beings and apes cannot be boiled down to one kind of sugar molecule.

We use roughly the same set of genes as other mammals, but we achieve different results with them. How can this be? If two sets of near-identical genes can produce such different-looking animals as a human being and a chimpanzee, then it seems superficially obvious that the source of the difference must lie elsewhere than in the genes. Nurtured as we are in nature–nurture dichotomies, the obvious alternative that occurs to us is nurture. Well, then, do the obvious experiment. Implant a fertilised human egg into the womb of an ape, and vice versa. If nurture is responsible for the difference, the human will give birth to a human and the chimp to a chimp. Any volunteers?

It has been done, though not in apes. In zoos, surrogate mothers have been made to lend their wombs to foetuses from other species in the cause of conservation. The results have been mixed at best. Wild oxen called gaur and banteng have been gestated in cattle, but until now they have died soon after birth. Similar failures have been achieved in wild moufflon gestated in sheep; bongo antelope in eland antelope; Indian desert cat and African wild cat in domestic cats; and Grant’s zebra in domestic horses. The failure of these zoo experiments suggests that a surrogate human mother could not carry a chimpanzee foetus to term. But they do at least prove that in every case, the baby comes out looking like its biological parent, not like its gestational parent. That, indeed, is the point of the experiment: to save rare species by mass-producing them in domestic animals’ wombs.³³

It is such an obvious outcome that the experiment seems pointless. We all know that a donkey embryo in a horse womb would develop into a donkey, not a horse. (Donkeys and horses are slightly more similar, genetically, than people and chimps. Like the two ape species, they also differ from each other in that horses have one more pair of chromosomes. This mismatch in chromosome number accounts for the sterility of mules and implies that a man mated to a female chimp just might produce a viable baby who would grow into a sterile ape-person with considerable hybrid vigour. Rumours of Chinese experiments in the 1950s notwithstanding, nobody seems to have tried this simple, but unethical experiment.)

So the conundrum only deepens. The genes, not the womb, determine our species. Yet despite having roughly the same set of genes, human beings and chimpanzees look different. How do you get two different species from one set of genes? How can we have a brain that is three times the size of a chimp’s, and is capable of learning to speak, and yet not have an extra set of genes for making it?