Genetics, medicine and ethics / by Zbigniew Bankowski

Genetics, Medicine and Ethics R esearch at present under way into the most basic aspects of human bio-logy - the genetic basis of life - presages a new scientific era, perhaps a revolution, in the medicine of the 21st century. It is opening up the possibility of changing the ways in which certain genes function in order to prevent or treat many of the diseases and dis- orders that are built into our cells from the moment of conception. This technology ~ the power to make such fundamental changes for the wellbeing of humanity - must not be abused, however. Human values, human dignity, must be safe- guarded. Society must see that the delicate balance between its ethical and unethical use is preserved. The CIOMS Conference on "Health policy, ethics and human values" (Netherlands, June 1987) and the Fifth "Summit Conference" on bioethics entitled "Hu.man genome sequencing: ethical issues" (Rome, April 1988) discussed this very timely issue. It is timely because of the decision taken recently to go ahead with the biggest biological research project ever undertaken, the "mapping and sequencing of the human genome" - the biological equivalent of the Apollo project to put a man on the moon. What is the human genome? DNA, or deoxyribonucleic acid, the "master molecule of life", is found in the nuclei of the cells of all living organisms - animals, birds, plants, bacteria, viruses . It consists of four chemical substances called nucleotides - namely , adenine , guanine, cytosine and thymine - together with a sugar.- deoxyribose - and phosphoric acid . It takes the form of two strands of these nucleo- tides twisted spirally around each The double-helix of DNA is the master molecule of life, and the DNA-based genetic code detennines what we are and who we are. WHO photos arranged by P. Davies WORLD HEALTH, December 1988 by Zbigniew Bankowski other in pairs - the "double-helix". In the nucleus of the human cell it is distributed along 23 pairs of chromosomes, rod-like structures which reproduce their physical and chemical structures through succes- sive cell divisions. It is segmented into units distinguished by unique arrangements or sequences and ratios of the four nucleotides. These units are the genes, and the human being has over 100,000 genes. The complete set of genes, unique to each human being, is called the human genome . It is repeated exactly in the nuclei of all the cells that compose the body, of which there are thousands of millions. If we can map every gene on the chromosomes that determine all our inherited characteristics. medicine will be in a position to change the function of those genes that give rise to dis- orders and abnormalities. Mapping of the exact location of genes on the chromosomes is the first step to be taken. After the genetic mapping is known, the next step is to determine the exact order of nucleotide pairs within the DNA molecule. The ultimate aim of the pro- gramme is to establish the map of the human genome in which the identity and location of each of the 3,000 million pairs of nucleotides will be known. Each cell has a particular function -to produce an enzyme which helps in the digestion of food , for example, or to produce a hormone, or to form muscle or bone or liver or brain. What each cell does and how it does it depends on the code laid down in the DNA, in the form of different arrangements and ratios of the nucleotides. All forms of life are coded or programmed in the same way. It is this genetic code that determines whether the living organism will be a rose , a bacterium, a whale or a human being. Similarly it is the genetic code that determines every characteristic that is inherited. Many inherited characteristics are influenced or shaped also by the environment into which the organism - the human being, animal or plant - is born and where it grows and lives. Such influences are climate, nutrition, education and occupation. They are influenced also by our understanding of ourselves and of others, our power of control over our lives, and our relations with other people. Sometimes genes are damaged and give rise to disorders or abnormal features . Some inherited defects are so damaging that the fertilised egg, the embryo, cannot develop beyond a period of days or weeks and dies and is aborted spon- taneously. Others give rise to more or less severe handicaps and the organism may survive in a favour- able environment or die early in an unfavourable one. Geneticists already have discovered the place on the chromo- some - the locus - and the function , as well as the internal structure, of hundreds of human genes or groups of genes . Hence it is now possible to predict from an examination of DNA on chromosomes, even before birth, a numbtr of genetic disorders. The recent research indicates a close relation between individual genetic patterns and susceptibility to develop a cancer, and a group of genes (oncogenes) has been identified. The detailed kn·owledge of the human genome will pro- foundly influence the understanding of human cancer development, the role of cancer risk factors and cancer diagnosis and, later, the approach to cancer prevention and therapies . It was also possible to establish that some types of diabetes mellitus, coronary heart diseases and muscular dystrophies are related to gene abnormalities. It is possible to envisage that the elaboration of the human genome will have, in the future , a profound 3 influence on medicine. At present medical practice relies to a great extent on a "probabilistic" approach where a diseased person is considered as an individual case within a diseased group. In the future diagnosis, prevention and therapy might be tailored to the unique genomic constitution of each individual patient. Genetic research is continuously adding to the list of genes of which their loci and functions have been identified. A complete map awaits the determination of the locus and structure of each of the genes that comprise the human genome. This would give us the basis for detecting unusual or abnormal features of individual genomes. Without a highly concerted effort it would take many years to map the human genome - that is, to discover and show the locus of every gene, or unit of DNA, on every chromo- some. However, genetic research is now so advanced that is has become feasible to do so in a relatively short time, provided the resources are made available. A committee of the National Research Council of the United States National Academy of Sciences has recommended that the mapping and sequencing of the entire human genome be undertaken immediately. The National Insti- tutes of Health of the US Govern- ment has been designated the coordinating agency for the project, which is expected to take at least 15 years to complete. Part of the work 4 is to be done in the US, part in Japan and part in Europe. The principal benefits would be, at least to begin with, in presymptomatic diagnosis of diseases, in determining predisposition to disease, and in drug treatment based on under- standing of gene function. Gene therapy, e.g., the replacement of defective genes by normal genes, may in time follow and grow in importance as a new and revolu- tionary field of medical therapy. With the continuing development of DNA technology, so far applied mainly to bacteria and other non- human forms of life, its application to medicine - to the prevention and correction of genetic defects - when the position on the chromosomes, the structure and the function, of each gene is known, can only be imagined. It will be revolutionary in the sense that, for the first time, medi- cine will be in a position to change the function or action of many genes or groups of genes that give rise to disorders and abnormalities . So far, medicine is concerned mainly with changing or countering the outcome or expression of genetic defects - insulin for diabetes, a special diet for phenylketonuria, beta-blockers for certain kinds of raised blood pressure; society pro- vides special education or institu~ tional care for certain handicaps caused by genetic error; genetic counselling helps affected people, or parents of affected children or M an should no longer passively accept his fate, for he is now able to orient his destiny towards rational becoming. Jean Dausset Nobel Prize in Medicine Left: A geneticist studies various model arrangements of . the human chromo- somes. Before long, it should be pos- sible to make a "map" of every gene - or unit of DNA - on every chromosome. Right Alike yet different. The study of identical twins helps scientists to detennine how genetic "programming" makes people look the way they do, while always remaining distinct indi- viduals. Photos WHO/P. Almasy and L Sirman© fetuses , make certain decisions. When the human genome is fully mapped and sequenced it should be possible to locate the origin of very many more genetic defects and dis- orders than is possible today. It may be, for instance, that antenatal care could include obtaining the map of the genome of the fetus, or that the routine medical examination of a sick or even well person could include that person's genome map. It would then be possible to determine who will get certain diseases, perhaps many years later, and offer the possibility of changing the action of certain genes in order to prevent such diseases, as well as to cure others. Genetic engineering It may be possible even to discover particular gene combina- tions that bring about particular characteristics, even particular kinds of behaviour, in human beings. This could open up the theoretical possi- bility of engineering genes, or groups of genes, to attempt to change certain physical or psycho- logical characteristics, with a view to " improving" the genetic stock- a form of "micro-eugenics" . How- ever, there are at present no sci- entific grounds for clafi:ning that this could happen, and it could not be justified on ethical grounds, Serious ethical issues arise in con- WORLD HEALTH, December 1988 nection with genetic engineering in medicine. Will individuals have the right to determine what may be done to their genes, or to their children's genes, to prevent or treat certain diseases? Does the individual have the right to know, or the right to refuse to be told, about genetic abnormalities which may cause disease years or decades later? May the genetic medicine specialist tell a young woman she should not marry a certain young man whose genomic map shows a defective gene which may shorten his life or would affect their children's lives seriously? Will the individual have the right to refuse to have her or his genome revealed? Will it be unethical to obtain an individual's genome map without her or his informed con- sent? Will parents have the right to refuse to have their children 's genome map revealed? Many views and aspects of human rights and dignity, and human values, must be harmonised - geneticists, the medical profession, ethicists, philosophers, theologians, lawyers, policymakers, and society at large should start to dialogue on the ethical aspects of the mapping and sequencing of the human genome. Clearly, all parties must have a say in regulating and con- trolling the ways in which this new knowledge and the technology are to be applied. Certain basic prin- ciples must be observed: respect individual autonomy or self~ determination; do good and not WORLD HEALTH, December 1988 harm; and ensure the just distribu- tion of benefits. Above all , the whole complex subject of "genome medicine" must be made sufficiently comprehensible to the lay public to enable it to be well understood , discussed rationally , and used responsibly for the welfare of humanity. The Fifth Summit Conference on Bioethics (at which WHO and CIOMS were represented) discussed these matters and submitted recommend- ations to the Summit Conference of the Heads of the seven most economically developed countries, held in Toronto in June 1988. These recommendations included the strong encouragement of research into the human genome and of rapid generation and dissemination of knowledge, while always protect- ing the rights and interests of those who are the subjects of such research. Gene therapy must meet the same rigorous standards of efficacy and safety as all other forms of experimental therapy. In particu- lar, the Conference pointed out, there can be no justification for gene manipulation of any germ cells involved in reproduction; this would have the effect that the altered gene would be passed on to the eventual offspring of the embryo, and thus involve a change in the genetic inheritance of future generations. The Conference drew attention to the need for the public at large and those in influential positions to be well-informed about the new dimensions of genetic knowledge and technology , especially to prevent its misuse. The new ethical issues related to " genomic medicine" need to be considered without delay. We must make all efforts to assure society that the exploration of the human genome will not interfere with human dignity. The continuous dia- logue between the scientists involved in research on the human genome, the medical profession, the ethicists, the policymakers and society at large on the ethical limits of applica- tions of new knowledge in this field is a necessity. In this connection it is imperative to inform the public at large through a continuous flow of information of the results of the study on the human genome in order to assure understanding and acceptance of this extraordinary progress in biology and medicine. Only then can we have assurance that the application of this fun- damental biological knowledge in medicine will be beneficial to human beings and the risks will be reduced to a minimum and well controlled. Clearly, the best guarantee of the responsible use of genetic engi- neering in medicine, and the best protection against its misuse, is a well-educated public. Genetics needs to be included in education, from primary school onward, if well- informed rational public participa- tion is to be assured in discussions and decisions about its use for the well-being of mankind. • 5