Nature via Nurture: Genes, experience and what makes us human. Matt Ridley
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