Germline Therapy Research Articles

Commentary: How Do We Think About the Ethics of Human Germ-Line Genetic Therapy?

The line between germ-line genetic therapy and somatic cell is more and more difficult to discern. With new abilities to effect germ-line genetic therapy it is less clear why such therapy should not be undertaken. Nonetheless, questions persist as to who is the patient in such therapy and about the extent of discretion that should be allowed prospective parents and the physician/researcher.

Genetic Disorders and the Ethical Status of Germ-Line Gene Therapy

Recombinant DNA technology will soon allow physicians an opportunity to carry out both somatic cell- and germ-line gene therapy. While somatic cell gene therapy raises no new ethical problems, gene therapy of gametes, fertilized eggs or early embryos does raise several novel concerns. The first issue discussed here relates to making a distinction between negative and positive eugenics; the second issue deals with the evolutionary consequences of lost genetic diversity. In distinguishing between positive and negative eugenics, the concept of malady is applied as a definitional criterion for identifying genetic disorders that could qualify for germ-line therapy. Because gene replacement techniques are currently unavailable for humans, and because even if they were possible the number of people involved would be quite small, the loss of diversity concern seems moot. Finally, we discuss the issue of iatrogenic disorders associated with gene therapy and discuss several 'real world considerations.'

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.

The shiverer mouse mutation shi/shi: rescue and preimplantation detection

The shiverer mouse mutation has been used as a model in this series of experiments. Germ-line therapy of this disorder has been demonstrated by producing mice transgenic for the wild-type gene for myelin basic protein (MBP). The mutation has also been diagnosed in preimplantation mouse blastocysts.

Legal Regulation of Human Gene Therapy

The adequacy of existing legal mechanisms to regulate clinical trials of human gene therapy is examined. Existing legal controls include the federal Guidelines for Research Involving Recombinant DNA Molecules and federal regulations for the protection of human subjects. Another significant mechanism is provided by judicial oversight, i.e., judicial decisions involving recombinant DNA research. Human gene therapy does raise new issues that still must be resolved. At least two weaknesses exist in the present regulatory system: first, Recombinant DNA Advisory Committee (RAC) only has authority over federally funded research, not work done with private support, and second, RAC is not mandated to focus on difficult ethical issues, e.g., germ-line therapy, that arise from human genetic engineering technology.

Human gene therapy: why draw a line?

Despite widespread agreement that it would be ethical to use somatic cell gene therapy to correct serious diseases, there is still uneasiness on the part of the public about this procedure. The basis for this concern lies less with the procedure's clinical risks than with fear that genetic engineering could lead to changes in human nature. Legitimate concerns about the potential for misuse of gene transfer technology justify drawing a moral line that includes corrective germline therapy but excludes enhancement interventions in both somatic and germline contexts.

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.

A Critique of the Enquete Commission's report on gene technology.

West Germany's Enquete Commission released its report on the prospects and risks of gene technology, Chancen und Risiken der Gentechnologie, in January 1987. Sass, a philosopher, criticizes the body for confusing ethics with emotion, and moral assessment with deep thinking, in its deliberations. In his words, the Commission's report "is a good case study for both forms of methodological and conceptual moral malpractice in matters of applied ethics." Sass identifies three methodological deficiencies that he believes led the Commission to reject many forms of genetic technology, in particular, germline therapy and research with human embryos: (1) moral assessment is based on the evaluation of worst case scenarios; (2) human life is identified with human persons; and (3) general terms like "human dignity" are applied to concrete situations for which the terms are too blunt and impractical.