Big plans for our blueprint

An 'exceptionally cautious' Ian Wilmut considers the pros and cons of regulation of genetically modified children next week's books focus will be education.

Shortly after the birth of our eldest daughter some 30 years ago, a salesman of encyclopedias visited us and showed us that the binding and paper were strong enough to withstand rough treatment by a child. He was counting on a natural wish of new parents to give their children every possible advantage. In future, however, if Greg Stock has his way, the visit would be to newly married couples and they would be offered instead the opportunity to "enhance" the abilities of their prospective children by genetic engineering. The motivation for the purchase would be the same.

Stock discusses a great variety of possible modifications, and comments that it would be easier to use existing methods to meet some needs. Since we can correct defective eyesight by use of lenses and select a different hair colour by use of dyes, why consider using genetic engineering for such purposes? By contrast, he supports the suggestion that it may be possible and desirable to change genetically children so that they cannot be infected by HIV.

Greg and I attended a meeting in Washington DC in the summer of 1998 when genetic engineering of children was discussed. As far as I recall, two concerns were expressed. In the first place it was agreed that it is essential that any procedure should be safe. In his book he accepts this, but does not define what is meant by safe. While I would join many others in supporting in principle the idea of correcting genetic diseases due to errors in one specific gene, I have grave doubts about other changes. Many traits are influenced by a large number of genes and, in turn, most genes will influence several characteristics. At present, it is not possible even to imagine how we might one day predict the outcome were we to change a gene involved in complex characteristics such as intelligence. Until we can make that prediction, any change would inevitably be an experiment, and I would reject the idea of taking a risk of that kind.

Second, in discussions in Washington there was an ethical doubt about imposing something on a child. It is intriguing to see that Stock describes his scheme as "self selection", which is certainly a misnomer. He seems also to believe that the ethical concern is addressed satisfactorily by the suggestion that molecular techniques could be used in the genetically modified child to undo the genetic change as the child produced germ cells (sperm or eggs), preventing the transmission to second or later generations. I am afraid I still do not see how you would explain to the child that it had been your intention to give them an added advantage by introducing only one change, while explaining that other changes had occurred unexpectedly. How would you be able to live with yourself? While I fully support research and the application of new technologies when they are possible and safe, I think we should be exceptionally cautious in applying new techniques in the production of children.

Whereas Stock makes a forceful and readable case that we should allow genetic modification of people at some time in the future, Francis Fukuyama provides a broader and deeper discussion and makes a case for an ethical framework to regulate these biotechnologies. Fukuyama considers a very wide range of biological opportunities. He has very little on the use of biotechnology in plants or in farm animals, but concentrates almost exclusively on new opportunities to understand and perhaps change human beings. Broadly, there are three sections to the book. First, the challenges and opportunities that will arise from biotechnology are outlined. Then there is a historical perspective giving different social approaches to the limitations and regulation of individual choice. Finally comes an outline of the basis on which the author proposes we make judgements about the future.

Each of the technologies is introduced with a historical perspective that will be very helpful to those new to the subject. As the author also views each issue with a questioning attitude from many different angles, most readers will find new insight into the social consequences of potential applications.

The first two aspects of biotechnology to be discussed involve the possibility of understanding and eventually modifying brain functioning. Fukuyama's historical review of the genetics of behaviour mentions in passing the ancient Greeks, Hitler, the restrictive Immigration Act of 1924 in the US and the systematic IQ test performed in the US Army during the first world war, before considering two analyses of the genetics of behaviour in detail.

Analyses of the behaviour of genetically identical twins brought up by different families suggest a significant genetic factor at work. But of course twins share more than their genes because they were carried in the uterus of the same mother. As a result, this analysis may overestimate the importance of genes in determining human behaviour. An alternative approach is to identify traits that are consistent across all cultures. But this approach is limited by the enormous cultural effect, so that it underestimates heritability.

We are entering an era when studies of specific genes will reveal their role. So far, most studies are of genes with clear effects in cases such as Huntingdon's disease. But as Fukuyama mentions, there are experiments in mice that demonstrate the effect of specific genes in memory function. Deletion of the gene-impaired memory - transfer of additional copies of the gene-enhanced memory - make the mouse more sensitive to pain. This is exactly the kind of unexpected effect that should make Stock pause for thought.

Fukuyama then turns his attention to genetic control of specific traits including intelligence, propensity to criminal behaviour and sexual orientation. He records the changes of scientific opinion and the way in which this has influenced political attitudes. From time to time he introduces questions to help readers define their own position in relation to a particular issue. Supposing that it were possible to prevent the birth of a homosexual child by the simple expedient of taking a pill at a specific stage of pregnancy, would you do so? This very brief outline of just one section will serve to demonstrate the very wide and deep survey of his subjects that are typical of Fukuyama's book.

The genetic revolution will permeate all of biology, including the development of new, more effective and specific drugs. Our attitude to existing drugs is often revealing, though. It is a shock to learn from Fukuyama that 10 per cent of American citizens take the antidepressant Prozac or a related drug.

This scientific section of the book is completed by a chapter on the prolongation of life through genetic engineering, which certainly raises very important social questions about the consequence of an ageing population. My general concern with this section is that it tends to accept too readily that a technical advance will become routine soon after it is first successfully attempted.

For example, the ability to introduce genetic changes into children through manipulation of embryos depends on at least three steps, none of which is yet routine in any species. One has to derive cells from embryos, to make precise genetic change in such cells and produce offspring by nuclear transfer from such cells. Several of the steps are possible in mice but at low efficiencies. But in rats, rabbits and farm species, no step is routine despite considerable research effort.

So the reader of Fukuyama should have in mind that the potential biotechnology he describes is at best several decades away and may not be practicable for a very long time. Similar reservations probably apply to most of the other uses of biotechnology he discusses. Nonetheless, I applaud his intention to prompt us all to think about the use and regulation of new biotechnology before it becomes routine.

In the historical review of social and legal attitudes to personal ethical choices that makes up the second section, the question becomes in practice:

"In the absence of divine guidance, how do you decide what is right and what is wrong?" Fukuyama dismisses the possibility, in a liberal democracy, that revealed religion could provide the basis for political choices. We are left with two alternatives. Either the law should intervene only to protect the rights of others who may be affected by the actions of an individual, or we need a regulatory framework. The author is an American academic steeped in a culture that emphasises personal freedom, but his distaste for the attitude is very clear. He is sharp in his criticism of modern philosophers, after Kant, and makes interesting contrasts between them and their predecessors such as Aristotle, Socrates, Locke and Hume.

In the final section, Fukuyama makes his case that biotechnologies should be regulated. He also suggests that in the US a new organisation may be necessary because existing bodies such as the Food and Drug Administration would find it difficult to extend their remit to encompass the new techniques. In this context, it is interesting to reflect that a century ago the sale of medicines in the US was unregulated. Pharmacists took the opportunity to sell medicines containing drugs such as cocaine that did not treat the patient's condition but made him or her feel more comfortable, at least for a time. It was as a result of protests, primarily by housewives, that laws were enacted to create what we now know as the FDA. Fukuyama's book may contribute to a similar kind of political pressure that will eventually ensure supervision of new biotechnologies.

It is a pity that Fukuyama's book has a sensationalist title. The phrase "posthuman future" seems to me fairly meaningless. But I recommend the book very strongly as one that will help the reader to develop informed opinions about biotechnology.

Ian Wilmut is head of the department of gene expression and development, Roslin Institute, Midlothian.