The development, during the last fifteen years or so, of techniques allowing increasingly sophisticated and accurate manipulation of DNA (whether of specific genes or sequences of unknown function) has generated many positive benefits. Thus, for a number of genes causing disease in humans, the position within the genome has been defined first as to the chromosome pair involved and then as to position within the specific chromosome. Such localisation permits important progress to be made in characterising the nature of the mutational changes involved in the disease genes themselves and, in cases where the function of the normal gene is poorly understood, in promoting understanding of its function and hence of improving treatment.
These molecular techniques have also helped greatly in the context of genetic counselling through the development of genetic probes. Probes enable the genome of an individual to be ‘interrogated’ as to the presence of specific DNA sequences such as a mutant gene which could cause a genetic disease in single or double dose. This approach is obviously very helpful when questions are asked about the possible presence of an undesirable gene in a developing fetus or, as in Huntington’s disease, where adults carrying the gene typically do not manifest this very severe condition until late in, or after, the reproductive phase of life.
In other areas of life different types of benefit arise. The technique of genetic fingerprinting, which depends upon the simultaneous scanning of a large number of related sequences, is an extremely powerful technique for resolving the scale of individuality of the genetic make up of humans (and many other species). The sequences scanned display so much variation between individuals (genetic polymorphisms) that, as with conventional fingerprints, all individuals are unique. Genetic fingerprinting has proved to be immensely valuable in a number of ways. Soon after the development of the technique it was used in a case in which the UK Immigration Service sought to deny admission to the UK to a child of a resident alien on the grounds that the boy was not her biological child. This was a difficult case particularly as the father was not available for testing. However the use of genetic fingerprinting established, with a very high degree of probability, that the boy was indeed the son of the woman concerned and a full sib of her other children. He was, therefore, admitted.
In recent years a significant number of cases of serious crime such as severe assault, rape and murder have used the technique of genetic fingerprinting to establish guilt or innocence of suspects or accused persons. DNA can be extracted from cells in blood, semen and saliva as well as solid tissue. Furthermore the PCR technique (polymerase chain reaction) enables information to be gained from extremely small samples of material such as a single fleck of blood, a hair root or even a single cell. The basis of PCR is that it amplifies the region(s) of interest in the DNA in an exponential way so that at the end of the operation a massive number of exact copies of the region of interest are available for analysis.
The PCR technique has also been applied successfully to mummified and fossilised material. Indeed very recently it has proved possible to determine some DNA sequences from a fossil weevil estimated to be not less than 120M years old.
The power of the technique of genetic fingerprinting has not gone unnoticed by criminals. In a case of rape in a rural area where external evidence pointed to the rapist probably being a local man, all males over the age of 16 living within a given distance from the scene of the crime were asked to give blood samples for analysis. The identity of the rapist was indicated initially not from the fingerprint which gave the final proof but from the fact that he attempted unsuccessfully to persuade a work-mate to impersonate him in donating blood.
A recent case in Arizona illustrates the utility of the technique in another way. The body of a murdered woman was found in the desert and one suspect was found to have a few seed pods of a palo verde tree in his pick-up truck. Genetic fingerprinting of these and of palo verde trees in the vicinity of the spot where the body was found established that of the dozen or so trees in this area only one tree (which had clearly suffered recent vehicle damage) gave a match. The suspect could not, on this evidence alone (even if he were the only driver of his vehicle), be said to be the murderer. However, he could with some conviction be said to have been close to the spot where the body was found for a significant length of time though in his statement to the police he denied being at the site on the day of the murder.
Some doubts have been cast on the intrinsic reliability of the technique of genetic fingerprinting and hence of its value in forensic work. These rest upon two possible sources of error. The first of these concerns poor experimental technique in deriving the fingerprint and clearly a good judicial system demands that only evidence derived from high grade and reliable techniques is admissible. The second cause for contention rests upon the fact that the resolving power of the technique is directly related to the number of genetic regions assayed. If a very large number, say in excess of 100, is assayed the demonstrable uniqueness of the individual is assured. If, on the other hand, a small number (say 3) is analysed there will be a significant number of matches in a population of, say, 10,000 individuals screened. In practice, in forensic work the number of regions assayed is sufficiently large to exclude identical genetic fingerprints in populations of 1 million or more occurring by chance, Thus, evidence presented in court tends to be of the form:
Such low probabilities are usually taken, without demur, to imply certainty of identification of the accused as the perpetrator. Where populations are subdivided into distinct ethnic groups or where small isolates (in which inbreeding takes place) occur the calculation of the probability of identity is fraught with difficulties. The calculations depend upon a knowledge of the frequencies of the different variant sequences in each region of the genome. Such frequencies will, in some cases, be significantly different in different ethnic groups. In isolates the extent of genetic variation is likely to be lower than that found in outbreeding groups and hence the probability of matches, within a group, by chance alone is increased. This will also be true for individuals within a family, a situation commonly of interest in serious crimes.
These difficulties of a statistical nature are undoubtedly real but, in my judgement, are likely to be of little practical significance except in isolated cases. Typically the effect that correction for ethnic heterogeneity has on probabilities is to change the probability of identity by chance of, say, 1 x 10-9 to 1 x 10-7. Nevertheless the prosecution would have a duty to show that any ethnic heterogeneity, family or other special factor had been properly considered where appropriate. The resolving power of the technique can always be increased by considering more regions of the genome.
The ability to characterise, locate and manipulate specific regions of the human genome also means that large and ever-expanding data files containing information on the genetic information present in individuals are being built up. Increasingly attention is turning to include not only genes which in themselves cause genetic disease but also genes which influence quantitative characters such as blood pressure or intelligence, genes which play a role in degenerative diseases of old age or genes which influence the risk of incidents such as strokes or ischaemic heart disease. The ethical issues raised by accumulating knowledge of this sort are considerable. At one extreme they involve the availability of knowledge of the genetic make-up of a child involving a gene which will cause a severe disease condition in later life. Who should be given this knowledge? What use should be made of it and when should this be done? Where should such information be stored? Who should have access to it?
At another level we may envisage a scenario whereby the premium structure of life assurance companies may assume a more sophisticated and discriminatory form such that if (through the lottery of the genetic shuffle at conception) individual A has a series of low risk genetic indicators and B as series of high risk genetic indicators for a couple of the more important causes of mortality their premiums for the same cover might differ by an order of magnitude. (In fairness the relative position for annuities should be reversed!).
We may note also that the improvement of economically important plants and animals by the use of new genetic techniques is already starting to benefit from the availability of genetic markers at molecular level for regions of the genome influencing characters like growth rate, yield and so on which may be expected to become of increasing importance in the next couple of decades. Transgenic techniques in which genes from one species or variety are incorporated by molecular (non-breeding) techniques into the genome of the variety to be improved are already contributing to new strains of plants such as tomato.
Transgenic techniques in humans are important for the process of gene therapy in which incorporation of normal genes into the somatic tissue of individuals suffering from a genetic disease is effected. A considerable number of clinical trials in several countries are in progress. While it is too soon to pass judgement upon the overall efficiency of the approach, some small scale work on diseases such as cystic fibrosis has given very promising results. On general grounds and based upon the data from animal experiments it might be predicted that success will be variable depending upon the specific disease condition and the protocol used but some may well be outstandingly successful.
It would not be surprising if, within the next decade, pressure arises in communities for gene ‘therapy’ of gametes or zygotes for genes influencing mental and personality characteristics in humans. Leaving aside technical and economic aspects, clearly there is a considerable social and ethical dimension to the consideration of such an approach. As research on the central molecule of life continues to generate results with a variety of applications the ethical and social problems associated with managing these applications in non humans as well as the human species are likely to become even more difficult to resolve.
J A Beardmore