Take, for example, Parkinson's disease, a neurodegenerative condition which causes a sufferer difficulties in moving, as well as severe muscle rigidity and tremor. In Parkinson's disease a specific group of cells towards the very base of the brain start to die, and the amount of the particular chemical (dopamine) that they use to communicate globally with remote systems and structures all over the brain starts to dwindle. Although stem cells could, in theory, replace the dying neurons and restore the levels of brain dopamine to normal, there is still a difficulty. Again, a transmitter, just like a gene, can contribute to more than one final function or trait. Although deficient levels of dopamine underlie the lack of movement that characterizes Parkinson's disease, excessive amounts of this same chemical can affect another brain system altogether and end up causing schizophrenia-like psychosis. If stem cells are implanted in the brain and start to release dopamine, how will we regulate the amount of transmitter that they release, so that the patient does not end up perhaps with better movement but now with crippling and terrifying hallucinations?
Another problem is that it is the business of stem cells to divide and proliferate into still more cells – so how might we ensure that the process does not get out of hand and result in a tumour, which is, after all, an inappropriate division of cells? There could be ingenious ways around this difficulty, such as ensuring by genetic engineering that the stem cells in question will divide only at temperatures a few degrees hotter than will ever occur in the real brain; but clearly the procedure needs to be improved. Then there are the non-trivial considerations – especially among the elderly – of the risk, expense and sheer unpleasantness of brain surgery. In summary, stem-cell implants into the brain may offer an exciting new development in the potential treatment of brain disease, but are far from ideal.
Another new approach to disease, based on the advances of molecular biology, is gene therapy. Gene therapy leapfrogs the unwanted product of a defective gene by inserting a new, well-behaved gene that can produce the ‘right’ protein into the chromosome. As more and more genes were identified over the last decade that could be linked to various diseases, so this approach seemed as exciting as it was obvious. However, things have proved far more awkward than initially hoped: one big difficulty lies in simply gaining access to the faulty gene, locked inside the nucleus at the centre of almost every cell in the body. And it is even more problematic to get the normal gene into the cell in a functional form. For many genetic disorders the defective gene is totally non-functional and makes no protein, but even in these cases gene therapy has not worked, due to the problems of entry and regulation. One option is to extract bone marrow, treat it with the engineered stem cells, and replace it in the whole person: over time the cells in the bone marrow will reproduce themselves, and gradually spread through the body. However, most effective would be a treatment whereby the new DNA could penetrate cells that did not have to be exported from and re-imported into the patient's body. As an alternative to using viruses, which are rebutted by our natural defence mechanisms, a new approach called biolistics is being developed: DNA is mixed with small metal particles, such as tungsten, then fired into a cell at high speed.
Other alternative approaches for gene therapy involve DNA encapsulated in liposomes (little parcels of fat), or injected into liver or muscle cells bound to calcium phosphate, which will help some cells take up the new DNA and express appropriately engineered genes. But it is proving very hard to get gene therapy to work, and it seems to be a less than ideal route for developing new therapies of the future. Rather than work with cells that are already set on their course to function in certain ways in the body, we could engineer the DNA in the infinitely fewer cells from which a person has yet to originate – in one egg or sperm cell.
Already sperm can be screened for gender selection. Male (Y) sperm are lighter, so they can swim better through thick solutions of albumin. Hence some claim that ‘male-enriched’ sperm can be made by filtering the ejaculate through such a solution. A female (X) sperm has more DNA (2.9 per cent), so it takes up more dye and thus gives off more fluorescence if irradiated with a laser. Here then is another means to detect gender prior to conception. Yet a further technique is to add molecular blockers (antibodies) specific to one or other gender that will then inactivate the sperm so targeted: X antibodies in the sperm would increase the chance of conceiving a boy, Y antibodies the chance of a girl.
In any event, conception outside the womb has opened up a wide range of possibilities that do not have implications for future generations but could still radically change the way we live in the future. Since 1978, when Louise Brown was hailed as the first ‘test-tube baby’, some 68,000 babies have been born in the UK alone using ‘in vitro fertilization’ (IVF), the fertilization of an egg outside the womb. Once the process has proved viable, and the fertilized egg (a zygote) has grown to some eight cells (the embryo), it is implanted in the womb.
The pioneering fertility expert Robert Winston used a gender screen to ensure, in one particular case, that a future embryo in an IVF procedure was a girl: as such she would carry an XX, and thus avoid a rare disease carried in her family and linked to the male (Y chromosome) line. Hundreds of diseases are linked in this way to the sex genes, and other genes relating to diseases, such as cystic fibrosis, are found on other chromosomes. So preimplantation genetic diagnosis (PGD), which Winston started in 1989, now screens for other diseases too. One or two cells are sampled a few days after conception, at the eight-cell stage of development of the foetus: the procedure has the potential to reveal any of the thousands of ‘genetic’ diseases that have been recorded so far, and therefore may well become more and more frequent, perhaps eventually even routine.
Once a screen shows up a problem, then currently that embryo is not used. Alternatively, as in the case of the anaemia victim Charlie Whitaker, screening could be used to select positively one embryo over another. And as we progress from screening for diseases such as cystic fibrosis, or Down's syndrome or spina bifida to screening for hardness of hearing or poor bone growth, where do we draw the line? Surely, as with all reproductive issues, this comes down ultimately to an informed choice made by the parents, and ultimately by the mother, as opposed to by doctors or governments or churches. Yet the big question still remains: whether the opportunities afforded by such powerful technologies will instil a new pro-eugenics mentality.
In the future techniques could also prove popular not just with infertile couples but with women who wish to establish their careers before having a child and yet still have a baby at the biologically optimum time. Below the age of twenty-five 95 per cent of women will conceive within six months of unprotected sex, whilst above the age thirty-five years of age less than 20 per cent do. We now know that the age – not so much of the mother as of her eggs – is critical for the chances of a healthy baby, and indeed of a pregnancy at all. Imagine therefore a scheme whereby a woman had eggs frozen at her biological optimum, say when she was eighteen years of age: she could then postpone pregnancy for as long as she wished, and still give birth eventually to the healthiest baby possible.
Now imagine that the young woman in question has her Fallopian tubes blocked so that she is infertile. Men could also take advantage of the scheme and have their sperm, along with the stem cells that make it, frozen, followed by a vasectomy. In so doing, men would be protecting themselves from the machinations of devious women aiming to trick the man into fathering a child. At last, half a century or more after the contraceptive pill was first developed, the link between sex and reproduction will have decreased to zero.
The implications of this are profound. If sex is just for pleasure, with no risk whatsoever of pregnancy, not even remote and covert at the back of our minds, then perhaps we shall engage in it with even less commitment than currently. A good comparison might be with the gay community: homosexuals have close emotional bonds and friendships but far more sexual partners. Factor in the cyber-technology we were looking
at earlier and it could well be that the act of sex becomes, like much else in the future, a passive hedonistic experience, where you ‘let yourself go’; meanwhile, personal relationships, where you have a clear identity and a clear role, be it with lovers, ex-lovers, friends or family, no longer include the escapist times of utter abandonment. Your personal life, with its plots and subplots, its complex inter-relationships, track records and histories, becomes a distinct and separate component to your existence – or, as a result of the new passive lifestyle of hyper-stimulation, starts to fade away…
In this increasingly compartmentalized existence, reproduction will rely more and more heavily on ‘in vitro’ techniques, like IVF, which take place outside the body. Further refinements of IVF can already, and will even more so in the future, circumvent causes of male infertility other than blocked ducts. If the problem is that the sperm cannot swim or that they are too few in number, then they can be injected straight into the egg, a technique known as ICSI (Intra-Cytoplasmic Sperm Insemination). And if sperm are not being manufactured at all, there is ROSNI (Round Spermatid Nuclear Injection), where precursors to sperm (spermatids) can be introduced into the egg and still fertilize it, using techniques now available for screening prior to implantation of embryos in the womb. The biggest reservation here is that the process avoids the normal test for sperm fitness: vigorous swimming towards the egg to establish the ‘winner’, in Darwinian terms of survival of the fittest. All these technologies for intervention at or around conception will undoubtedly enable us to live and work in a different way, and to have ‘healthier’ children. But where does health end and a quest for physical and mental perfection begin?
‘The elements so mixed in him, that Nature might stand up and say to all the world, “This was a man!”’ says Mark Antony of Brutus in Shakespeare's Julius Caesar. Surely it is our very imperfections, and the ways we deal with them both in ourselves and others, that have kept poets, novelists and historians in business for millennia. If screening is taken to the limit, then a homogeneous society where everyone, but everyone, is super-healthy and mentally stable (barring any traumatic life events) could occur; a situation that is hard to imagine from our current perspective of a humanity with a mass of imperfections. The extreme, especially if coupled with the less taxing cyber-relationships we have been discussing, will inevitably be humans with ‘less’ Brutus-type human nature. On the other hand, we have already seen that genetic technologies may well transform physical health below the eyebrows; but when it comes to the brain the elimination of diseases, let alone the ‘enhancement’ of normal mental prowess, will be far more difficult.
Yet it is not just our future progeny for whom genetic intervention will affect health, life expectation and relationships. Those of us who will soon be the new grey generation may not remain untouched by the hand of molecular biology. We saw earlier how a healthier lifestyle and dramatic modifications to it, such as calorie restriction along with far more effective monitoring, would stave off many of the diseases with which we are currently familiar. However, the more developed the society in which we live the more hereditary factors appear to dominate in determining our lifespan, over nutritional and other environmental issues.
One idea is that ageing is due to dysfunctional senescent cells releasing potentially toxic substances on to other cells as they slowly deteriorate. One anti-ageing strategy, then, would be to introduce a killer gene that became active within a cell once that cell was showing signs of sickness: this sudden death would be safer for the body than a slow demise that could affect all the neighbouring cells. Another possibility is to exploit the age-defying actions of the enzyme telomerase. As we saw in Chapter 2, this enzyme can prevent the ends of chromosomes in the nucleus of each cell from fraying, by preserving the shoelace-type caps, telomeres, that otherwise deteriorate with age. Normally telomerase operates only in stem cells, cancer cells, and sperm and eggs, where – for good or ill – the chromosomes need to be in tip-top condition; the idea would be to engineer all the ordinary (somatic) cells of the body so that their genetic profile could remain equally pristine.
Although ageing might be tackled using genetic technologies, it does not follow that we would necessarily live for longer than the 100 years or so that seems to have remained a constant maximum throughout history – it's just that more of us would do so. But were a specific ageing gene to be identified then presumably modification to said gene might enable us to live, for the first time, for appreciably longer than ever before. It has been quite a few years now since Seymour Benzer identified the ‘Methuselah gene’ for fruit flies, which enabled them to live a third longer than their non-genetically enriched counterparts. However, it would be quite another matter for such a gene to exert its dominance in the complex bodies of humans. More likely, ageing is comparable to intelligence or sexual orientation: there is a complex genetic component, but one that is highly and continuously interactive with the environment. Ageing, like mental prowess, is not a simple single phenomenon but rather an umbrella term covering myriad events.
Nonetheless, a society in which most people lived to be 100 years old would be very different from the one in which we are living now. The first issue would be whether the older generation were active, or helpless and in need of constant care – and the proportions in which these two very different constituencies co-existed. Then there would be the predicament of a physically debilitated individual who still had an active mind, or the reverse: imagine being physically fit, but with a brain that could no longer register what was happening around you. In any event, career structure, political organizations, allocation of resources, family structure, retirement schemes, housing, work and leisure activities would all be skewed by a shift in society where the post-reproductive sector was the majority. But perhaps even that assumption of an end to fertility should be challenged. After all, we can now produce clones from adult mammals.
Within the next few decades the technique of cloning humans should be established sufficiently to satisfy the qualms of those who argue that as yet the results are too variable for complete confidence that the procedures can be considered safe and reliable. After all, the prototype clone, the sheep Dolly, was the only success out of 277 fusions of eggs with the genetic material, the DNA, from an adult udder cell. The reason why Dolly was such a breakthrough was because, until she proved otherwise, adult DNA was considered to be no longer able to re-enter into cell division. This discovery of how to switch adult DNA back on and clone from adult cells (far harder than from immature ones) opened the door to cloning dairy animals with high milk or wool yields, to which end most work on cloning has actually been directed. As well as the production advantages of a uniform, healthy stock, animal engineering can now make vital medicines and products for human health, such as the protein lacking in one form of the disease emphysema, or lactoferrin, the source of iron in mothers' milk.
Cloning really just means copying, and copying genes as DNA raises no ethical issues. It is only cloning people that raises problems. Accordingly, there are several types of cloning. ‘Molecular cloning’, of just a few genes, is mainly a research tool that need not bother us here. Nor will we spend much time on the cloning of embryos that will remain, for the most part, as embryos; stem cells from such embryos could combat disease, whilst embryos could also be cloned for IVF procedures so that a woman does not need to undergo the discomfort of repeated cycles of egg harvesting. Whilst the issue of using human material in this way as a source of spare body parts is far from trivial, most controversy is generated by the idea of cloning as an infallible treatment for infertility – be it cloning an existing child, a third party or indeed, as 7 per cent of respondents in a recent Time magazine survey would wish, oneself.
The immediate reflex objection to cloning, as to artificial insemination in the 1930s and IVF in the 1970s, is that it is ‘not natural’. The standard rejoinder to this argument, often lodged against many scientific developments, is to question what is ‘n
atural’. Taking an aspirin for a headache, for example, would not qualify, nor having a broken leg put in plaster, and certainly not having a heart transplant or an artificial heart. On the other hand, there are no medical reasons for intergenerational cloning; it is solely an issue of social preference, personal priorities and the choice of a small number of individuals.
A more specific objection, however, is that sexual reproduction in the normal way allows the possibility that the offspring will have useful traits for dealing with a new environment not apparent in either parent. Maybe, but no one is suggesting the whole of humanity switches to reproduction by cloning. It is hard to see how the continuation of our species on this planet will screech to a halt if a cloned baby is born to a desperate childless couple, or to a committed and loving same-sex couple. There are, in any event, already 48 million clones alive and well – identical twins; as geneticist Gregory Stock points out, the world does not seem the poorer for their being among us. The same twins could also stand as a counter-example to those objecting to cloning on the grounds that it is important to have genetic uniqueness. Moreover, there are many children who favour one parent very strongly, in looks, say, rather than the other; a cloned child, on the face of it, literally, would be no different.
These objections, and indeed the flights of vain fantasy, that arise in the cloning debate are based on the mistaken time-worn assumption – yet again – that genes are autonomous components of brain function, and that they will dictate exactly how a clone feels, thinks and acts up to the point of being a perfect simulacrum of the original. We saw earlier that genes have a part to play in brain operations but are far from being autonomous or predominant in the emergent mental traits. And at best, you could only ever have a cloned daughter or son – always you, the adult, will be separated from your clone by a generation, and that generation difference will mean a world of difference in culture, fashions, diet, health and education. You will hardly be more exactly like your cloned offspring than you would be like a child conceived conventionally who strongly resembles you, and certainly you will probably be more different in character from your clone than from your identical twin, born in the same generation.
Tomorrow's People Page 17
