pp. 381-383 in
Bioethics in Asia
Editors: Norio Fujiki and Darryl R. J. Macer, Ph.D.
Eubios Ethics Institute
Copyright 2000, Eubios Ethics Institute
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F9. Bioethical Aspects of Medical Applications of Human Genome and Gene Therapy Projects in Russia
Vladimir I. Ivanov.
Research Centre for Medical Genetics, Moscow, Russia
Large scale international study on human genome mapping and sequencing will lead to outstanding changes in medical genetic practice. Former a posteriori probabilistic conclusion on the genetic health of next children gives way to ever earlier (up to preconceptional period) deterministic identification of certain sequences in the genomic DNA of any person. Already employed procedures of DNA sampling are simple and safe, however very much complicated ethical, social, and legal problems arise of an access to and of the proper use of the personal genetic information generated in the course of genetic testing and screening.
A national Human Genome Project started in Russia in 1989. From the very beginning, the project included medical genetic studies subdivided into four blocks, arbitrarily designated as gene pathology, gene diagnosis, gene therapy, and bioethics. Since 1996 a gene therapy block has also been included into another already elaborated National Project known as Medical Problems of National Priority. The accumulated data on the features of morbid genes in populations of Russia enabled to modify the known methods of DNA identification, respectively, and thus to increase the precision of DNA-diagnosis in this country of some two dozen genetic diseases (see Table 3 in paper 8.2 in this book). This, in its turn, facilitated to provide genetic diagnosis to several hundreds of families at risk and to estimate the incidence of several most frequent genes in the populations of Russia.
Thus, data on human genome fine structure and function have ensured a breakthrough in technologies available for medical genetic practice. Former probabilistic inferences on the genetic health of the members of a family of known risk gradually give way to a precise deterministic identification of respective DNA segments in any family member. In general, already employed procedures of DNA sampling are simple and safe. However, clinical application of these new approaches generate some ethical, social, and legal problems concerning the access to and the proper use of the genetic material and the genetic information involved and/or produced in the course of genetic testing and screening.
International experience and debate on the problems has helped to reach a consensus on the following items:
- privacy and confidentiality of sensitive information are to be respected in any situation;
- use or disclosure of genetic information is to be based on the informed consent of the testee;
- it is the medical professionals' duty to explain to their patients all the relevant details and consequences of the procedures performed.
The increasing ability to manipulate human genotypes and phenotypes through gene therapy is leading to difficult and equivocal questions about permitted vs. prohibited procedures. Claims about the eugenic alteration of mental and emotional traits determining the behavior are challenging human self-understanding and the capacity of social institutions to respond adequately.
In Russian human genome and gene therapy projects diverse approaches to gene therapy of cystic fibrosis, Duchenne muscular dystrophy, growth hormone deficiency, some genetic diseases of blood and marrow cells are elaborated. In some labs first attempts to deal with hypercholesterolemia and some cancers are also made.
In general, gene therapy complies with the therapeutic concept of medicine. Introduction of recombinant DNA or recombinant-DNA-derived human proteins is to replace their pharmacologically active counterparts which cannot be isolated from their natural source. The biotechnological procedures used for this purpose are friendly to the environment by using raw materials from renewable sources, low energy consumption, and producing biodegradable products only. So, recombinant DNA technology and biotechnology offer the opportunity of providing new therapeutic principles of high ethical value.
Gene therapy is a complex multistage technology including construction of recombinant-DNA vectors, transfer of the constructs to patients' target tissues, care for the patients. At any stage, hazards caused by the constructs to personnel, patients, third parties, environment are to be considered. In comparison with physically and chemically based therapies gene therapy is better vectorized to reach target tissue alone. However, it still faces many drawbacks, such as selectivity, specificity, sensitivity, and safety of gene transfer.
Among a variety of issues regarding potential uses and abuses of recombinant DNA technologies related to gene therapy there is little disagreement on the use of somatic gene therapy, which has gained broad approval, but there is much controversy over the use of germ-line therapy: practically all who were evaluating the related ethical aspects wanted to ban its medical application on grounds of fundamental and pragmatic considerations. However, even in somatic gene therapy a spontaneous inclusion of therapeutic DNA into patient's germ cells cannot be totally excluded. Therefore, practicing gene therapy one has to follow the rules for general medical genetic service that any manipulations are to be based on informed consent of the patient and his/her family, that privacy is to be given top priority, and that confidentiality of sensitive information is to be unequivocally respected.
Gene therapy is still an investigational modality that requires thorough patient care planning and monitoring for inevitable unexpected side effects of administration of genetically engineered medications and new routes for delivery. There is an increasing need for clinical personnel to understand gene therapy so that they can educate patients and families. To keep pace with new discoveries, the personnel need to update their knowledge of genetics and learn the fundamentals of recombinant technology.
Medical ethics institutionalized with clinical activities being determined by the patient's interests as they developed in the doctor-patient relationship. The ethical nature of the health concept was emphasized in the positive definitions of health such as the one by the WHO. The established goals for clinical intervention surpass the effective medical capabilities. The curricula of medical schools will have to be reviewed in light of these goals. We characterized the contemporary values and the way medicine has adapted to them: superspecialization and doctors' change in social image brought about by the impact of technocracy in clinical activities, increasing costs of medical care, the interference of non medical managers in the process of clinical decision, litigation and breaches of confidentiality. Technical and social developments lead to new ethical problems in which the moral principles of the doctor can be confronted with patients' demands in situations of difficult choice. Contraception, abortion, genetic engineering, transplantation, cloning,, the expansion of drug dependency and euthanasia are examples of problems that clinicians frequently face today.
In spite of all the complexity, pluralism, and controversy of the notion of ethics in diverse religious and philosophical systems, there always is an invariant essence expressed in some Testament or a Code of just conduct aimed at maximum benefit and minimum harm to involved persons and the community, as well as protection to those handicapped due to effects of hereditary and/or environmental factors. Any such code is based on a set of ethical principles, which reflect both the cultural history of a society or a nation in question, and the general laws of social behaviour of Homo sapiens. Considering rapid recent progress in knowledge on human genome, as well as in manipulation with and artificial alteration of human somatic and germ cells, medical geneticists have to look for an acceptable solution of two interrelated problems: (i) what rights to intervention into human development and reproduction they have, and (ii) what are the tolerable risks that they may generate applying ultrafine modern DNA- and cell-technologies?
Some approaches to formulation of a professional consensus-based ethical code in terms of "new genetics" may be illustrated by the "Declaration of Inuyama" and recent documents of the sort elaborated by the UNESCO, the Council of Europe, the WHO and a number of national bioethical committees.
Rather soon, cell and DNA sampling from affected persons, carriers, and family members with subsequent storing and cloning of the material for screening, diagnostic, and prognostic purposes will become in many countries a routine procedure involving quite considerable proportion of individuals in human populations. Then, an already arisen question of who is to be regarded as the proprietor and legal manager of the biosamples and the genetic information they hold will become quite urgent. Unlike any part or component of the body in situ, explanted and in vitro propagated cells, as well as experimentally deciphered nucleotide sequences of their DNA seem to cease being sole and inalienable property of the individual of origin. But, since both the sampled substance and the information therein can be either properly used to the good of, or misused to the harm of, the donor or some third party, a sort of "Social contract" is needed regulating the rights (privacy and confidentiality included), the interests, the benefit, the obligations, and the protection of all the persons involved, as well as the society as a whole.
An agreement concerning the access to confidential genetic information requires thorough regulation of who is authorized to collect the information, how it is to be stored, maintained, and/or linked to other data banks, and the last, but not the least, how the data are used or released for free or privileged circulation. The subtleties of gene combinations in a pedigree, as well as complicated physical and chemical mechanisms of DNA replication, mutation, and metabolism are not easily understood by a layman, so it is a professional's responsibility to ensure informed patient's consent to perform any genetic diagnostic and/or treatment procedure.
Of especial importance is the confidentiality of information concerning DNA lesions found in particular persons. On one hand, the disclosure of such information may cause direct harm to the proband; on the other, its withholding may lay obstacles to safe reproductive behaviour and to prevention of new cases of the genetic disease in question among already living or yet to be born members of the pedigree.
In any case, a physician and a geneticist are obliged to explain to a patient and his/her family, full truth about their condition, so as to provide due options to choose the most appropriate behaviour and medical procedures. It is also the professional's duty to present the genetic information in such a way as not to encroach upon the patient's right of moral freedom, which (in respect of own genome organization) means the right to know or to refuse to know about morbid features of his/her genotype.
People of Russia , including both the lay people and the medical professionals, are not, as yet, well accustomed to medical genetic services and modern procedures. Respectively, ethical and legal aspects of the service are now in statu nascendi. Up to now, only ethical and legal issues included into RF Basic Legislation on National Health Care and Ministry of Health Guidelines on Medical Genetic Service are available. However, due to current progress in reproductive and genetic technologies, the legal and ethical implications of the latter are being widely discussed in the society and by the professionals and authorities. The Federal Law, regulating the handling of non-human genetic material and constructs, is already in action. The draft bills concerning human reproductive rights and the bioethical regulation of application of modern biomedical technologies are now at the stage of seeking input from professional and social expertise.
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