People's Democracy

EVER since Watson and Crick discovered the structure of the human DNA in 1953, scientists have speculated that the future of medical diagnosis and treatment would lie in the mysteries hidden in this structure. The human DNA, as we know today, is a twisted (double helix) structure made up of by sequences of different kinds of chemical building blocks. Sequences in the strands of this structure are called genes. It is these genes, which contain coded information that determines individual characteristics of a living organism, and also determine how the living being will react to its environment. Genetic information is thus encoded by the structure of deoxyribonucleic acid (DNA) and the sum total of this information for any organism is called its genome. The study of the genome is termed genomics.

Two major changes in our understanding about the cause of disease highlight the importance of genetics. First, any disease process, whether it is the virulent properties of a microorganism that enable it to invade tissues or the pre-cancerous changes in the respiratory tract which follow years of exposure to tobacco smoke, can be explained ultimately in terms of chemicals that are released in the body. Specific chemicals, in turn, are released through signals received from specific genes. It is also now understood that there is a degree of individual variation in interaction with environmental agents (whether they be physical agents like smoke or living agents like bacteria). This too is genetically determined. Thus an understanding of the actions genes should help us better understand the underlying pathology of disease.

Before continuing, however, it needs to be emphasised that the study of genetics should not lead us to a position where we conclude that we are completely at the mercy of our genes and have no control over our destinies. What we are today is determined by a complex interplay between our genetic make-up, our environment and the cultural milieu in which we are raised. Our genes are but one, albeit important, part of this complex interplay.

The announcement of the success of the Human Genome Project last year has given an enormous impetus to this new field of biological and medical research. Almost the complete sequence of the three billion chemical building blocks, or bases, of the DNA which constitutes the human genome has been determined. Genes determine our characteristics and the way we function through the medium of information they carry to make functional products - most often proteins. It is currently estimated that the human genome contains between 28,000 and 40,000 genes. Though it is clear that it will take a long time to determine the function of all of them, it is believed that the information that will be generated will have a profound effect on the provision of health care in the future. But it is equally clear that it will raise new sets of ethical issues, which have not been encountered before in medical practice.

A report released by the World Health Organization, recently, titled:

Genomics and World Health focuses on the potential of genomics to alleviate human health, as well as the potential problems associated with its use. The report points out that the reality that much of the advances in genomics were made, and in part are owned, by the developed world give rise to the concern that a genomics divide will be created that will further widen the equity gap in health between rich and poor nations. The report argues that genomics and related technologies should be used to narrow the existing unethical inequities in global health but points out that this would be impossible in a situation where over 80 per cent of investments in 2000 and DNA patents in genomics in the period 1980-93 are held in the United States. The report also emphasises that genomics brings with it complex and new ethical, legal, social, and economic implications as well as concerns about risks and hazards. Issues that are being thrown up include those related to confidentiality, stigmatisation, and misuse of genetic information. These have the potential for creating a genetic underclass (i.e. those perceived to have "defective" genes) that would be denied medical insurance.

Intellectual property rights associated with DNA sequences and the potential exploitation of populations in developing countries by creating genetic databases, often at the behest of companies based in the developed world, are other areas of major concern that are described in the report. Despite the tremendous potential and promise of genomics, it is impossible to predict when its benefits for health will be realised. The Report suggests that it is vital that developing countries continue to maintain focus on the basics of what can be done now, particularly in the fields of public health and the development of more functional healthcare systems. At the same time, however, the Report recommends that developing countries must prepare themselves for this new technology and carefully explore its possibilities, always looking at its cost effectiveness in comparison to more standard approaches to medical care.

Many areas of concern are listed in the Report, in relation to the use of genomics to treat genetic diseases. Because the tools to tamper with the natural evolutionary process are now available, this may have an impact on human evolution itself. For example, there are concerns regarding the possible long-term ill effects of using recombinant DNA technology to control and treat genetic diseases. These concerns are based on the notion that in our attempts to help families or individuals with a genetic disease we may increase the number of deleterious genes in the human gene pool. Further, preventing parents who are carrying the same genetic defect from reproducing, and hence having affected children, will tend to interfere with the normal evolutionary mechanism for reducing the frequency of deleterious genes within a population. In offering similarly affected parents the possibility of prenatal diagnosis and termination of pregnancies of affected babies, and thus encouraging them to have children, more carriers of deleterious genes will be produced. However, it will take many generations to produce any significant change in the frequency of genetic diseases in the population by these interventions, and most geneticists do not feel that current technology offers a serious risk to the human gene pool. However, if it becomes more widespread it is something that will have to be monitored carefully.

Moreover, the successful development of germ-line gene therapy (i.e. treatment aimed at genes that are present in the cells responsible for reproduction) might have a more immediate effect on the human gene pool. It is being argued by many scientists that germ-line gene therapy, because its effects will be passed on to successive generations, should not be allowed to go forward. The Report suggests that it is important to distinguish whether germ-line therapy is now sufficiently safe to be permitted from whether it could become so in the future. At present, it is not possible to remove and replace a gene at the correct place on the chromosome. Instead, it must be delivered on a crude, imprecise vector that may generate unintended genetic effects with unknown risks.

Moreover, some of the research necessary to limit these risks may require human experimentation that would be difficult to perform ethically. For these and other reasons there is widespread consensus that germ-line gene therapy, because its potential harmful consequences would be passed on to future generations, should not be permitted at the present time, even in the case of serious genetic disease. The risk-benefit ratio of germ-line interventions would be even less favourable in the case of less serious genetic disease or in the case of genetic enhancement (i.e. when it is used not to prevent a disease but to create favourable characteristics like fair skin or taller people). However, it is possible that at some point in the future gene therapy may have progressed to the point at which germ-line gene therapy, particularly for serious genetic disease, promises a sufficiently favourable risk-benefit ratio to warrant its use. When it is clearly desirable to prevent serious disease in a particular individual, it could likewise be desirable to prevent that disease in future generations as well. The Report concludes that this would be an argument against imposing a permanent ban on germ-line gene therapy.

Another area of concern listed in the Report relates to Genetic Databases. These databases are being created to make available to researchers a pool of genetic information from population with varying characteristics. Concerns relate to access to genetic information from such databases, both by individuals themselves and by third parties. The latter might include health insurance companies, government bodies, or the legal profession and police. Hence a great deal of attention is being paid to the questions of confidentiality and access to these databases.

Although much effort is being put into protecting individuals there are still possibilities for the misuse of the databases. It has also been suggested that genetic research based on these collections may have the effect of stigmatizing entire countries or particular groups of individuals, and there are concerns about commercial exploitation without adequate compensation. Also, because scientific research depends on freedom of access to samples and information, the commercial ownership of these databases may have a deleterious effect on genetic research.

Another major issue about the establishment of large-scale databases is that some developing countries are establishing collections of this type, often at the behest of companies from the developed world. The Report says that because of the lack of appropriate regulatory and ethical bodies in some of these developing countries these problems become much more serious and the dangers of inequitable commercial exploitation are even more acute.

One other major concern highlighted in the Report pertains to patenting of genetic information contained in the DNA of any living organism. The Report laments that despite the fact that DNA sequences represent naturally occurring information patents continue to be granted. Although the US Constitution allows discoveries as well as inventions, in current practice patents are not supposed to be allowed on discovery. For a patent to be granted in either Europe or the USA, an invention must be novel, show utility, and be capable of industrial application. In practice, however, these criteria do not seem to be met in many cases. The Report says that on balance, the current position regarding DNA patenting is retarding rather than stimulating both scientific and economic progress. The Report says that, "the monopolies awarded by patents on genes as novel chemicals are not therefore in the public interest" and concludes that, "this unsatisfactory situation has important implications for the health of the developing countries".