Germline Interventions Research Articles

The Ethics of Human Genetic Intervention: A Postmodern Perspective

Gene therapy for a particular disease like Parkinson's involves ethical principles worked out for other diseases. The major ethical issues for gene therapy (and the corresponding ethical principles) are safety (nonmalfeasance), efficacy (beneficence), informed consent (autonomy), and allocation of resources (justice). Yet genetic engineering (germ-line interventions or interventions to enhance human potentialities) raises emotions and fears that might cause resistance to gene therapies. Looking at these technologies in a postmodern perspective helps one to appreciate the issues at stake in social and cultural change with a new technology such as gene therapy. While “modern” technology and ethics have focused on the autonomy of the individual, we are beginning to see a lessening of such emphasis on individualism and autonomy and more emphasis on the health of the population. Such a social change could cause technologies about which society may currently be cautious (such as human genetic interventions) to become more acceptable or even expected.

"Playing God" and germline intervention.

The phrase "playing God" so popular with journalists takes on a serious meaning in the debate over germline genetic intervention. While guarding against the dangers of human pride implied in the phrase "playing God," special attention is given here to the Christian concept of the human being as created in the divine image, the imago dei. Human beings are dubbed "created co-creators." In this light ethical arguments proscribing germline intervention are examined and refuted, leaving the door open for creative responsibility on the part of the present generation for our future progeny.

Cultural and individual risk perception in human germ-line gene therapy research.

New technologies find friends and foes, and have to work their way into the fabric of moral values and cultural attitudes. Nuclear energy, information technology, and gene technology are the most prominent technologies of our times with different cultural, national, and international approaches. They are the black powder, steam boilers, and locomotives of our times. Their moral and cultural control and acceptability requires moral assessment on the following six levels: individual, familial, religious, societal, national, and international. National and international guidelines must protect individual human and civil rights while at the same time avoiding forced transnational and transcultural uniformity. National and international instruments, therefore, must respect different religious and cultural attitudes towards the manipulation of life, concepts of disease and disorder, risks in human experimentation, and the identification of the appropriate agents to make moral choices based on available therapeutic technologies. I will briefly focus on the cultural diversities in assessing moral risk in germ-line research and on identifying the moral agent best qualified to make germ-line intervention decisions.

Germ-Line Gene Modification and Disease Prevention: Some Medical and Ethical Perspectives

There has been considerable debate about the ethics of human germ-line gene modification. As a result of recent advances in the micromanipulation of embryos and the laboratory development of transgenic mice, a lively discussion has begun concerning both the technical feasibility and the ethical acceptability of human germ-line modification for the prevention of serious disease. This article summarizes some of the recent research on germ-line gene modification in animal models. Certain monogenic deficiency diseases that ultimately might be candidates for correction by germ-line intervention are identified. Several of the most frequently considered ethical issues relative to human germ-line gene modification are considered in the context of professional ethics, parental responsibility, and public policy. Finally, it is suggested that there is merit in continuing the discussion about human germ-line intervention, so that this technique can be carefully compared with alternative strategies for preventing genetic disease.

Human Germ-Line Therapy: The Case for Its Development and Use

The rationale for pursuing the development and use of germ-line selection and modification techniques is examined in this essay. The argument is put forth that it is the moral obligation of the medical profession to make available to the public any technology that can cure or prevent pathology leading to death and disability, in both the present and future generations. Society should pursue the development of strategies for preventing or correcting, at the germ-line level, genetic features that will lead to, or enhance, pathological conditions. Because prenatal screening and even early embryo screening and selection can prevent only a subset of known genetic disorders, direct genetic intervention is the only way in which certain couples can exercise their rights to reproductive health. Finally, the arguments most often raised against the pursuit of and use of methods for germ-line intervention shall be discussed.

Human Gene Therapy and Congress

Congress was the scene of conspicuous debate about human gene therapy during the 1980s. Congressional interest was sparked primarily by concerns about germ-line gene therapy expressed by clerics and public interest groups. The initial debate was provoked by Martin Cline's misadventures in 1980 and rekindled in 1983 by congressional resolution against germ-line intervention sponsored by Senator Mark Hatfield. The first hearing on gene therapy was held upon the release of the President's Commission report Splicing Life, in November, 1982, before a House subcommittee chaired by Congressman Albert Gore, Jr. Representative Gore later requested a report on gene therapy, which was released by the Office of Technology Assessment in December, 1984. He also sponsored the legislation that established the Biomedical Ethics Board and Biomedical Ethics Advisory Committee, Congress's abortive attempt to reestablish a federal bioethics commission. Implications of advances in human genetics, including gene therapy, were to be among the first topics addressed. Congress passed no substantive legislation affecting gene therapy research or clinical trials, but served principally as a national theater for debate. If and when germ-line gene therapy is contemplated, Congress will be faced with difficult choices, but will likely take no action to block trials that appear safe and are intended to produce clinical benefit for particular individuals.

Germ-line gene therapy and the clinical ethos of medical genetics.

Although the ability to perform gene therapy in human germ-line cells is still hypothetical, the rate of progress in molecular and cell biology suggests that it will only be a matter of time before reliable clinical techniques will be within reach. Three sets of arguments are commonly advanced against developing those techniques, respectively pointing to the clinical risks, social dangers and better alternatives. In this paper we analyze those arguments from the perspective of the client-centered ethos that traditionally governs practice in medical genetics. This perspective clarifies the merits of these arguments for geneticists, and suggests useful new directions for the professional discussion of germ-line gene therapy. It suggests, for example, that the much discussed prospect of germ-line therapy in human pre-embryos may always be more problematic for medical genetics than adult germ-line interventions, even though the latter faces greater technical difficulties.

Gene transfer into mouse embryos.

Gene transfer into the murine genome was accomplished nearly a decade ago by use of chimeras and teratocarcinomas; however, the low frequencies of transfer into the germ line and other difficulties stemming from mosaicism and karyotypic abnormalities in chimeric mice have limited the general usefulness of this procedure in achieving transformation in mammalian embryos. The introduction of cloned genes into teratocarcinoma cells, selection for a mutant phenotype, and transfer of those cells into mouse embryos holds some promise as a technique to employ mouse chimeras for gene transfer into mice. Infection with animal viruses and retroviral vectors provides another way to introduce exogenous DNA into mouse embryos. Infection with Mo-MuLV has been utilized to characterize the relationship between sites of integration and gene function in developing and adult mice. Gene transfer by microinjection of cloned recombinant DNA has been used by many laboratories for the transfer of DNAs into mouse embryos. The factors affecting transformation frequencies and sites of integration are unknown at present, although it seems that integration is not strictly mediated by homology-dependent events. Many genes have been introduced into mouse embryos by these procedures and many of these are expressed at high levels in appropriate tissues. No realistic possibility exists at the present time for the utilization of embryo gene transfer in the medical field for the correction of genetic defects for several reasons. First, in order to effectively provide "gene therapy" it would be necessary to determine the genotype of each recipient egg, a technical impossibility. The genetic diseases that would be amenable to germ line intervention are recessive diseases and there would be only a 25% chance of any one embryo derived from heterozygous parents being a homozygous recessive. Moreover, it would be impossible to distinguish the normal from abnormal embryos. Second, the frequencies of transformation are so low as to exclude work on human beings on ethical grounds. Third, the parameters effecting chromosomal integration sites and gene expression have not been fully characterized. Until it becomes experimentally possible to target the newly introduced DNA into expressable chromosomal sites and actively replace or supplement defective genes, the possibility of gene therapy through manipulation of embryos is remote. Yet, efforts to provide gene therapy in somatic tissues have been promising, leading to expression of a modified phenotype (Anderson, 1984). In contrast to embryo gene therapy, gene therapy in somatic tissues would not lead to germ line propagation of the manipulated genotype.(ABSTRACT TRUNCATED AT 400 WORDS)