Robin McKie 

Children of the revolution

In the future will we be able to design our offspring, determine their height, hair colour, temperament even? Some experts think it's only a matter of time. But even if we perfect the biotechnology, should we really begin to 'play God'? Robin McKie, The Observer's science editor, analyses the latest experiments and ponders the ethics.
  
  


It's a science fiction writer's dream: people made to measure, a society of perfect biological specimens. And one day, it is claimed, this brave new world will be upon us. Our descendants will live free of illness and inherited weakness. The day of the designer child will have arrived.

To some it is a prospect to be cherished; to others a nightmare. Either way, it cannot be avoided for long because the science of genetics is advancing at a startling rate. Doctors are already using the techniques of modern molecular biology to add and subtract genes from future generations. The question is: where will it stop?

The answer, according to enthusiasts such as Lee Silver of Princeton University, is that it won't. Although practical difficulties abound, the urge to have healthy children is so strong that the science of human engineering will be driven inexorably. As he points out, two key approaches to the shaping of a child's genetic make-up are already being perfected by scientists. One - embryo selection - is now routinely practised by doctors. The other - embryo engineering - is still in its infancy but should be practicable in the near future.

Selection involves creating embryos from a woman's eggs and her partner's sperm using the techniques of in vitro fertilisation. Each embryo is allowed to develop for a few days until it has grown into a cluster of a few dozen cells. One cell is then removed, broken up and its DNA contents tested for the presence of a particular gene. Those embryos that pass muster are placed into the womb, and pregnancy allowed to progress to term.

This is a boon when dealing with conditions such as cystic fibrosis, the West's most common inherited disease. In the past, there was little parents could do, even if they knew the condition ran in their families. Today they can test foetuses in the womb and terminate affected pregnancies - or they can exploit embryo selection. Using IVF, several embryos are made and tested. Those that do not carry the disease are then placed in the womb and allowed to go to term.

This technology is now winnowing out some of mankind's most damaging inherited conditions, among them blood disorders such as thalassaemia and sickle-cell anaemia, wasting muscle afflictions such as Duchenne muscular dystrophy, neurological ailments such as Huntington's chorea and various mental defects. So whether we like it or not, genetic science has already begun to shape future generations.

Taken one step further, scientists are now finding ways to use embryo selection to pick individuals best suited to withstand problems that might assail them beyond childhood or adolescence. Chicago's Reproductive Genetics Institute recently helped a 30-year-old woman with early-onset Alzheimer's disease to have a child who lacks the trait and who can therefore face a future unsullied by the prospect of dementia. Other teams have begun screening women susceptible to breast cancer so that they can have children that do not carry the gene that predisposes them to the condition.

Then there is the gene called CCR5. Those lucky enough to possess one variant of this gene are less likely to become HIV positive. Those with two copies appear to be virtually immune to the disease. The CCR5 gene is therefore a prized totem. The trouble is that, in the West at least, HIV is no longer considered such a terrible threat, certainly not one that is currently worthy of being adopted as a criterion for embryo selection. 'At the moment CCR5 screening is unlikely to become commonplace,' Silver admits. 'But that could change if Aids became a much greater danger.'

Elsewhere in the world of genetics, ethical debates are raging on all fronts.

Creating sibling donors

Should parents be permitted to create a child who could save an ailing elder brother or sister? An example is provided by Linda and Jack Nash from Englewood, Colorado, whose first child Molly suffered from Fanconi anaemia, a fatal disease that attacks bone marrow. The couple went through five cycles of test-tube fertilisation before producing in 1999 an embryo that was screened, found to be clear of Fanconi anaemia, and whose tissue matched Molly's. Scientists led by Dr Yury Verlinsky, a geneticist at Chicago's Reproductive Genetics Institute, then removed stem cells from the baby's umbilical chord and transplanted them to Molly, who was then six. These replenished her marrow and Molly now seems free of the disease thanks to her baby brother Adam. 'It came to me that God created Adam and took his rib to create woman,' says his mother, Lisa. 'The rib is the source of marrow, and it saved Molly's life.'

Sibling selection is not without critics. 'There is a disturbing utilitarian connotation overshadowing the parents' decision,' says Edward Wallach of Johns Hopkins University of Medicine in Baltimore. 'In effect, this infant has been forced to donate his cells, which some might consider a form of child abuse.' But distinguished Oxford geneticist Sir Walter Bodmer counters: 'If a child is wanted and loved and saves another's life, is this wrong? It is not obvious that it is.'

Following the Nash family's success, British couple Michelle and Jayson Whitaker asked permission to produce a tissue-matched sibling for their son Charlie, who suffers from Diamond-Blackfan anaemia, a rare blood disorder which means he must have a transfusion every three weeks. Britain's Human Fertilisation and Embryology Authority (HFEA) refused. Tissue-matching is not a sufficient reason to attempt embryo selection, it states. So the Whitakers §ew to Chicago and went through IVF and pre-implantation screening. Last July Michelle gave birth to James - a perfect tissue match for his brother. A decision to go ahead with the stem cell transplant - which carries a five per cent risk of death - has still to be made by the family.

The crucial criterion in these examples is medical need. Every example of gene selection to date has been done to correct an ailment or eliminate it from future generations of a family. But what can be done for parents who want, say, tall children, or boys only, or blond-haired offspring: characteristics selected for social not medical reasons? The answer at the moment is very little. The authorities, in particular the HFEA which controls genetic screening in this country, strongly disapprove of such desires.

Sexing the embryo

A classic and highly contentious example of social selection is provided by embryo sexing. Some of us have strong preferences for either a male or female baby but have to make do with the lottery of conception when a man's Y chromosome - which confers maleness - is passed on randomly to 50 per cent of embryos, like flipping a coin with the same uncertain outcome.

There is one exception to this disapproval of embryo sexing, however. In diseases such as haemophilia and Duchenne muscular dystrophy, victims are nearly always male, and so doctors treating affected families are permitted to test embryos and implant only female ones, thus preventing the disease from manifesting itself in the next generation. (Intriguingly, as females are carriers of such conditions, this process will not stop the disease being carried on to affect future generations.) Picking a child's sex using embryo technology for any other reason is forbidden in Britain.

But for how long, ask researchers who point to the recent setting up in Fairfax, Virginia, of the company MicroSort which offers customers a chance to pick the sex of their next child - not by embryo selection but by sperm sorting.

MicroSort's researchers have developed a technology that allows them to differentiate sperm that carries the X-chromosome (which confers femaleness) from sperm that bears the Y-chromosome. Using an instrument called a modified flow cytometer, heavier sperm, carrying the X chromosome, are separated from lighter, Y-bearing sperm. The technique is said by MicroSort to be 91 per cent effective if a girl is wanted, and 75 per cent if a boy is sought. So far several hundred babies have been born in this way and several dozen are believed to have come from British parents.

Crucially, this technique does not employ embryological procedures and is therefore not covered by Britain's human fertilisation laws. MicroSort could open a clinic in the UK, though for how long it could operate remains uncertain. The HFEA, having launched urgent public consultations on non-medical sex-selection in Britain, is soon to adjudicate on the issue of sperm-sorting. Most experts expect them to seek a ban.

Certainly, there is a powerful case for wanting to stop couples succumbing to 'gender stereotypes' by picking the sex of their children. The country would be afflicted by the sudden release of repressed patriarchal urges bent on ensuring a male-dominated society, it is argued. So let people continue to take their chance in the lottery of life, say opponents of sex selection, or face the prospect of legions of men baying for the attentions of a few, suppressed women who would end up being sold to the highest bidders.

It sounds alarming but such scenarios are not supported by the facts. Last month researchers from the University of Geissen reported, in the journal Human Reproduction, that almost a quarter of Britons would have no qualms in selecting their children's sex. At the same time the vast majority indicated that they would like to have an equal number of boys and girls in their families. 'Much of the opposition to social sex selection is based on the assumed danger of a sex ration distortion due to a common preference for boys over girls. But according to our surveys, this assumption seems to be unfounded,' said Dr Edgar Dahl, leader of the research project.

In fact, the study indicates that most people would like to select a child's sex mainly to keep their families balanced. Juliet Tizzard, of the Progress Education Trust, a UK charity that promotes research on genetics and reproduction, comments: 'What is so wrong about paying to have a girl after you have had four boys?. That is scarcely going to distort society.'

One response by opponents to sex selection is to invoke the 'slippery slope' argument. If we start to tinker with the genetic make-up of future generations, who knows where it will end. One day we will be picking our babies' sex, the next will be selecting eye-colour, height, intelligence, looks, temperament, personality, musical ability, mathematical prowess, preference for the music of Led Zeppelin, desire to support Everton, and countless other attributes. The joyous random nature of creation will be destroyed, replaced by made-to-order children.

Embryo engineering

All the selected attributes we have discussed have been ones possessed by their natural parents - thus revealing the key drawback of embryo selection. It is limited by the genes that two prospective parents already possess. Professor John Harris of Manchester University stresses: 'You can't give an embryo traits that their parents don't already have.'

Scientists can only seek variants of one or two genes when selecting embryos. Yet for attributes such as height, intelligence and musical ability, dozens of genes may be involved. Silver explains: 'Suppose you want to ensure your child is as tall as possible, and if we assume height is controlled by 10 genes, five in the mother and five in the father, then the rules of genetics indicate only one in a thousand embryos that you create will carry the set of genes that ensures maximum height. That is an awful lot of embryos to create and discard just to gain a couple of inches in height for your child.'

Enter the new science of embryo engineering. Take a genetic characteristic from outside the family - a couple of genes for extreme tallness, for example - and add this to the make-up of the embryos you have created. Your child will grow up straight and true. Just like that.

But this takes us far beyond embryo selection and into the far more distant, more troubling business of embryo engineering and its partner technology, gene therapy, a technique in which a new gene is added to an existing individual's entire set of genes (or genome). Scientists have succeeded in modifying animals in this way, creating sheep and goats that make human medicines in their milk, and animals that are susceptible to human diseases which can then be tested with new drugs. But the technology is largely hit and miss. Countless embryos are created and destroyed before a successful, genetically engineered creature is produced. Experiments on such a scale on human embryos is currently viewed as unacceptable by most governments.

Nor have trials of human gene therapy on adults provided great encouragement, much of the difficulty stemming from the fact that scientists use genetically engineered viruses to carry a particular gene into the bodies of their patients. Sometimes this can cause severe problems, as occurred at the University of Pennsylvania in September 1999 when Jesse Gelsinger, an 18-year-old patient with the rare disorder called OTC deficiency, died after the infusion of a genetically modified cold virus into his diseased liver. In the wake of his death, a series of professional lapses at gene therapy labs were uncovered, and the technique's reputation has suffered accordingly.

Yet genetic science has progressed with astonishing rapidity in many other areas, in particular the Human Genome Project in which scientists, working at breakneck speed, have unravelled all three billion units of DNA that make up the human genome. More human secrets are being uncovered as scientists search through the project's results, more ways of improving our DNA are coming to light and more pressure is mounting to do something about the consequences. 'We have created genetically engineered mice by adding genes to mouse embryos, so we know that the technique is ultimately practicable, though obviously a lot of safety issues have to be overcome,' says Silver. 'We therefore have to face the prospect that at some point, someone, somewhere - perhaps in 20 years - will cross the line and create a genetically engineered human embryo that will grow up to be a living human.'

What will drive this process is the discovery of DNA that confers protection against major ailments such as cancer, heart disease or depression - genes like the variant of CCR5 that protects against Aids. The urge to ensure our children have healthy lives is deep and ingrained, and geneticists who offer ways to aid that will only fuel the desire to ensure those advances are passed on.

Nor is the methodology remote. Scientists at several universities and biotechnology companies are developing artifcial chromosomes made of human DNA, leading to the prospect of one day developing tiny bags of human genes that could be injected into embryos so that they grow up with the ability to express new life-enhancing proteins. But who would get these new genes? Who could afford them?

'I think for a basic chromosome package that improves health and staves off illness, society should pay,' says Silver. 'After all, it will benefit through reduced medical and hospital costs and increased productivity from its citizens. After that, for packages for beauty or athleticism, for example, individuals would have to pay.'

To many people, such an idea raises the prospect of creating two classes of genetic 'haves' and 'have-nots', the former being able to afford to have designer children. Silver remains unworried. Such shifts would take dozens of generations to manifest themselves, he says.

Others object that producing children with strikingly different characteristics from their parents is unnatural, an issue seized upon by Harris. 'Why do so many people believe children should be like their parents?' he asks. 'It is difficult not to view this desire as a form of ethnic cleansing, and smacks of the pressure so many cultures put on its members not to "marry out" or mate with members of another tribe.'

Many other researchers counsel caution. 'I think we should be very careful about this,' says geneticist Steve Jones. 'Anatomy began in the sixteenth century yet it took us another 400 years to carry out the first transplants. Today we have only just begun to isolate genes. We should not expect to be able to transplant them overnight. In any case, if you really want to engineer your child's IQ, stick to the old ways. Send them to Eton. And if governments want to improve the nation's intelligence, the best value for money would be to double teachers' salaries.'

Silver is unapologetic, however. 'People say we should not be doing things that are unnatural, but nature can be really nasty. We just want to take the sting out of its tail.

And while we wait for fact, here's fiction

The idea of designing a self from scratch - with the opportunity to create a face, body, temperament - has long been a favourite conceit of artists (or indeed of hack writers and film-makers). Naturally, the ways of constructing these freshly-minted souls have shifted in tandem with shifts in technology. So that Frankenstein's monster, given life by Mary Shelley in 1816, now seems very much like a nuts and bolts affair of the Industrial Age.

John Frankenheimer's brilliant, underrated Seconds (1966), featuring a 'perfected' Rock Hudson, carries all the speed and neuroses of the Sixties. By the time we get to Weird Science (1985), the John Hughes-directed comedy, the central creation is computer-generated, a 'cyberbabe' confected to please a pair of young hi-tech anoraks.

When the late Stanley Kubrick first started to prepare Artificial Intelligence: AI, cloning and genetic engineering might have seemed still largely in the realms of fancy. But by the time Steven Spielberg brought the film to the screen in 2001, after Kubrick's death, the ability to design babies - in a post-Dolly The Sheep world - seemed much more possible. In Gattaca (1997), Ethan Hawke played genetically imperfect, and the new governor of California, Arnold Schwarzenegger, got in on the act in The Sixth Day (2000), as several incarnations of the same man.

Playing God is ideal for cinema, lending itself to glorious sci-fi visuals. But it's perhaps a sign of how anxious we are becoming about the potentials of new biotechnologies that the finest writers are now engaging with the subject. Margaret Atwood in Oryx and Crake, her latest novel, sketches a future of genetic screening. A future that appears far from perfect.
Carl Wilkinson

 

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