Tomorrow's People

by Susan Greenfield

  But sexuality, and indeed gender stereotypes, do seem to have a strong ‘natural’ basis. I remember having a drink with friends whilst their son, oblivious to us boring adults, played with his trains; his sister, however, also of pre-school age, force-fed me peanuts, already engaged in a three-year-old's version of nurturing. And a more formal,

  unambiguous demonstration of gender-linked tendencies can be seen on a video of pairs of 7- and 8-year-olds ostensibly passing time in a waiting-room that contained a range of toys. The little boys start playing immediately, competing with each other in various games, and restricting conversation mainly to directives and scores. For most of the pairs of little girls, however, the toys are secondary to establishing a relationship, finding out how many siblings they each have, what they are going to be when they grow up, and so on. And almost every parent with whom I have discussed this issue will avow that their sons have a different way of behaving, somehow ‘wired-in’, that is distinct from that of their daughters.

  More formal studies show clear differences in attention span, verbal learning, construction ability and many other skills between girls and boys. Arguably, the book Men are from Mars, Women are from Venus was such a bestseller because much of the adult gender-based behaviour it described was all too familiar. If sexual orientation is just part of the general gender-related features of mental function, then it is clear that some biological switch must be thrown, if not in a single gene then very early on in life, to determine it.

  The current consensus is that brains are sexualized within the womb according to the levels of exposure to the male hormone testosterone, linked to the Y chromosome. This testosterone will have many effects both on the structure of the brain and its subsequent operations. A little like the protein that, in a very indirect way, affected memory, so varying levels of testosterone are necessary but not sufficient for determining an individual's sexual orientation. Many other factors, including other genes, are involved, whilst testosterone itself contributes to the expression of other traits, such as aggression.

  So what sense can we make, after all, of the notion of a gay gene? In industrialized society only 1 per cent of men are exclusively homosexual, whilst some 5 per cent are bisexual. Yet bisexual men have double the ejaculation rate of heterosexuals and a larger number of partners, including more women. In his lifetime a bisexual man is therefore likely to inseminate more women than a heterosexual man. At the moment bisexual men and women are in a minority because a variety of factors, including the risk of disease and physical or verbal attack from homophobes, militate against activities other than heterosexual ones. In the future, however, if the constraints of both prejudice and disease are removed, the numbers of bisexuals will escalate, according to biologist Robin Baker, due to an unfettered dissemination of their gene profile via their more active and diverse sex lives.

  Nonetheless, one prediction is that in the future couples could vet the genes of their embryo for particular traits; homosexuality may prove to be a characteristic to screen against on a par, say, with baldness – harmless enough but not particularly desirable. On the other hand, it might equally well be the case that bisexuality becomes the norm; since the nuclear family may be due to fragment completely, and if AIDS and other related health hazards can be removed, an ambiguity of sexual orientation, a blurring of conventional roles, could well reflect the increased and more generalized tendency for a less rigid, less stereotyped sense of self.

  One final example of an alleged single gene ‘for’ a complex mental trait – indeed one that featured in my newspaper today – is of the gene ‘for’ crime. The idea that criminal tendency could be inherited gains credence from a study of 3,586 twins from the Danish Twin Register: identical twins had a 50 per cent chance of sharing criminal behaviour compared to a risk of only 21 per cent among non-identical twins. Similarly, a much studied Dutch family, with a repeated history of violence, would suggest that the problem might be genetic.

  One approach to the issue of the gene for violence lies in examining the relation of genes to brain chemistry. The tendency towards violence could be due to an impairment in certain genes controlling a particular enzyme that, in turn, regulates the availability of a particular chemical messenger, a transmitter. This hypothesis is all the more attractive in view of the fact that mice with a similar chemical defect also seem to be very violent. However, this situation is just like that of the protein related to memory in neuroscientist Joe Tsien's experiment, or like the contribution of testosterone to sexuality. Once again there is a component chemical that is all-important in the final function or dysfunction, just as a sparking plug is vital to the function of a car. But there is far more to a car than a sparking plug, and indeed a precarious sequence of events between ignition and the movement of the vehicle. So it is with genes and brain function.

  Although genes are identifiable as unambiguous entities, they are not at work incessantly and autonomously: a variety of constantly changing influences will switch them on or off from one moment to the next and will thereby determine whether a particular protein is to be made, and indeed exactly what type of protein it actually is. Many factors, such as the age of cells, their development and, most importantly, their immediate chemical environment, will determine whether a gene is activated at any one time. The seething micro-environment of chemicals within the cell will itself be influenced by macro-environmental factors, chemicals that seep into the fluid-filled spaces between the brain, which are in turn influenced by what is happening in the rest of the body, and beyond, in the outside world.

  In the case of the brain, a vital element will be the ceaseless communication from neighbouring cells, as transmitter signals stream onto each neuron. Since we have some 1015 brain connections, the physical junctions between one neuron and another will outnumber the entire number of genes by some 1010. And the type and amount of transmitters in active service at any one moment will be determined by the operations at that particular instant within large-scale circuits of neurons that make up different brain structures – which in turn will be influenced by what is happening both within the rest of the body and ultimately to the individual as they interact with the outside world. The relation between brain functioning and the chemicals that underpin it, and even more so the genes that make the proteins that make those chemicals, is as convoluted, remote and capricious as in the old verse ‘For want of a nail’, which traces how a nail missing from a horseshoe led to the eventual loss of a kingdom. Yes, there was a causal relationship, but that link between the loss of a nail and the result of an armed combat is so indirect and tenuous that it is surprising that it was identified at all.

  This subtle dialogue between nurture and nature can be seen in action in a recent experiment by Colin Blakemore and his colleagues in Oxford: they were investigating the influence of the environment on the disease Huntington's Chorea. Huntington's Chorea is a severe disorder of movement, characterized by wild, involuntary flinging of the limbs; hence its name, from the Greek for ‘dance’. It is an example of a disorder of the brain that, unlike Alzheimer's or schizophrenia or depression, can be blamed on a single gene. Normally, within this gene, one particular sequence of three (triplet) component chemicals repeats itself over and over again, up to twenty times. But if the number of such repeats increases to thirty-nine, then the disease appears in an individual in their mid sixties; forty-two repeats and the patient will be afflicted by their forties; fifty repeats and they will be ill by the time they reach their thirties. The greater the number of repeats the earlier in life the disease strikes. Surely here, then, the cause of the disease is entirely genetic and we can justifiably talk of the ‘gene for’ Hunting-ton's Chorea; could this disease be the exception that tests the rule of a constant interaction between nature and nurture?

  Blakemore and his colleagues were working with ‘transgenic’ mice, so called because they had been engineered to have the faulty gene ‘for’ Huntington's Chorea: their performance in tests of thei
r limb control would therefore be certain to grow worse with age. But surprisingly, despite the clear relation between gene and illness, it turned out that the mice could be protected enormously by environmental stimulation, by exposure in early infancy to mouse toys – playthings which provided an extra opportunity to interact and explore. The performance of the mice was nowhere near as dramatically impaired, nor did the disability start as early, if they had experienced a certain kind of lifestyle.

  We can see from this type of experiment that a gene is not an independent or autonomous agent. Instead, it is a component of the brain that may or may not be triggering production of a protein at any one time. As such it works within the context of the whole brain. When a gene is activated it makes a related chemical (messenger RNA), which acts as a template for the construction of the specific sequence of amino acids that will eventually constitute a much larger molecule, a protein. But segments of this mRNA can be spliced out before the particular protein is made, so that some ‘edits’ give different products from others. The number of different combinations of mRNA segments multiplies enormously the potential for what each gene might ‘do’. In one case, in the fruit fly, a single gene could be the ‘gene for’ a staggering 38,000 different proteins! And then the same protein can be transformed into something different and varied after manufacture: depending on whether it was incorporated as a component into some aspect of the more complex machinery of the cell, or was perhaps coated with sugars to form up to any of some 200 chemical groups, its ‘function’ would change. Small wonder that despite the nugatory number of genes we have – remember, 80,000 at most – our bodies are making and using millions of different proteins.

  This discrepancy between number of genes and number of proteins, not to mention all the nested anatomical and functional hierarchy of the brain in which we have just glimpsed those proteins at work, accounts for why it is usually naive and misleading to expect to extrapolate from a single gene to a complex mental trait, such as IQ, homosexuality or criminality. Even when the ‘cause’ is inherited, many genes are at work and in incessant dialogue with non-genetic factors in their environment. Hence we should not be too surprised to learn that different genes work differently in different species – for example, a mutated, breast-cancer gene causes mice to die as embryos, whilst in humans everything is normal until well into adulthood. Even in yeast, which has only 6,297 genes, the pattern of protein manufacture of more than 300 of those genes will alter as a result of a single mutation in a single gene. Contrary to some current thinking, then, genes do not set any agenda or have minds of their own, nor do they perform one job only in autonomous isolation.

  Nonetheless, just because genes have to be put in their place their huge potential for new types of medication is by no means negated. By understanding how any one gene triggers the manufacture of a particular protein, new types of drugs can be developed that are proteins themselves. As well as insulin, which has been in use for many years for early onset diabetes, there are now new treatments using human proteins for wound healing and blood-vessel growth. Currently there are only 400 to 500 molecular targets for drugs; in the case of mental dysfunctions, the main treatment strategies work at any one of the different successive stages (synthesis, action and removal) to change the final availability of the chemical messengers, the transmitters. However, during the next decade, because of the potential advances in the genetic sciences, there will be a massive explosion of new types of targets, to some 4,000. These new drug targets will enable diagnostics, protein replacement and the use of drugs (monoclonal antibodies) that combat the undesirable effects of certain proteins by direct molecular interaction with them.

  But on the other hand, we won't be able to trace easily how a normal function is ‘caused’ by a particular gene, just because we can correct a faulty component and therefore help cure a dysfunction; just as you will never work out how a complete engine functions by contemplating a sparking plug placed by itself on a table, simply because the replacement of a faulty sparking plug will enable you to drive your car again. We can work backwards from a dysfunction to the cause, and fix it. But we cannot work forward from a single factor or component and expect to understand the whole system. There is therefore a massive difference between gene-related treatments for certain illnesses and vague hopes for enhancement of a complex mental trait. This point is a really important one, if we are to evaluate and predict how far the new advances in genetics are going to take us in our lives in the 21st century. Some innovations are just around the corner whilst others are pure fantasy, for good or evil.

  Imminent gene-related development could change our lives in the very basic area of paternity and fertility testing. Paternity testing is already in extensive use for resolving situations where the identity of the father is a critical issue. The basic principle is to reveal the particular, unique pattern of the DNA that flanks our genes. This technique is 100 per cent accurate, and because it is so reliable the likelihood – an urban myth places it currently at 10 per cent – that a man may be unwittingly ‘fathering’ another man's child is zero.

  But why should all fathers not be entitled to the same assurance? By making the paternity test universal and obligatory at the time of birth society will be able to ensure that every man knows exactly his responsibilities, or lack of them. In his visionary yet chilling The Future of Sex, Robin Baker reasons further that it would be fairest to tax fathers, irrespective of whether they stayed with their families or not. After all, a child costs the same sum to bring up whether the father is not there at all, a commuter dad who sees his child for a few hours a week, or there all the time. By introducing a universal child tax for biological fathers, Baker believes, we would have a much more equitable state of affairs. All genetic children would have an equal financial share from their father, according to their age but irrespective of whether or not they were his first or second family. Only in this way, Baker asserts, will we have a just society where no mother is simply abandoned nor any man duped; and it is only possible due to the science of genetic fingerprinting.

  A possible downside of this arrangement is that a woman could ensnare a wealthy man or two as a meal ticket: if paternity testing was compulsory, proven paternity would guarantee an income for eighteen years or so. A problem for a woman relying on this scheme would be the ‘time wasted’ seducing such well-off candidates for fatherhood without knowing definitely whether she was in the fertile part of her cycle. Hence a further reason – up until now – for the nuclear family: the man and woman need to stay together so that they can copulate on a monogamous and genetically accountable basis over an extended time frame, since neither can be exactly sure when the woman is fertile. Because sperm can live in the female's body for up to five days, we need to anticipate ovulation up to five days in advance, and as yet that has not proved possible. But if, as predicted, such testing was to become infallible, then for the first time ever an unwanted conception would be more costly for the man than the woman. In order to justify the current nuclear family, in reproductive terms, the woman must gain help from the man in raising that family, whilst the man must be unable to tell if the woman is fertile. In Baker's scenario, thirty or so years from now obligatory paternity testing and an infallible fertility predictor would, in combination, remove both those factors.

  But the genome era will affect far more than our reproductive habits. One of the most immediate benefits could be new treatments for disease based on stem-cell therapy. Stem cells are the basic, generic cells from which other, more specialized cells develop, according to the biological environment in which they are placed, be it bone marrow, or heart muscle or brain. These highly versatile and premature cells can be generated artificially at later stages in life by cloning: the process whereby the nucleus of an unfertilized egg (i.e., most of its own DNA) is removed, and the DNA from an adult cell is introduced instead. This cell and the empty egg are then fused together such that they divide to yield ‘stem cells’, from which eve
ntually nerve cells, heart-muscle cells, skin cells, bone and blood cells will all be elaborated. Clearly replacing organs with these cloned, forerunner cells is a very attractive idea: it circumvents the ethical difficulty and time delay of obtaining donor organs (the donation itself is uncertain, the timing completely unpredictable, and the relatives of the deceased may have to give permission when already in considerable distress).

  Of the many applications of stem-cell therapy, a recent project that particularly captured journalists' attention was a technique pioneered by the biotech company ReNeuron, who plan to implant stem cells into areas of the brain damaged by stroke or neurodegenerative disease. Data from animal experiments is promising, and the technique offers hope for disorders for which there is currently no effective treatment. However, it is hard to estimate the damage that may be caused to brain tissue by the implant as it is pushed into its correct location deep within the brain, and it would be equally difficult to measure how well these alien cells could eventually replicate the intricate wiring of the normal cells in an adult system. No one will volunteer to act as a control – to undergo a sham brain operation, whereby the conditions of anaesthesia, and indeed the whole surgical operation, are identical to treatment, but an inert substance is implanted instead of stem cells. Even when the cells are implanted, and in the correct place, it will be hard to know how to regulate what they then proceed to do.