“Prevention” and the Goals of Genetic Medicine

Abstract

Authors participating in the renewed discussion of germ-line gene therapy have begun conflating two senses of the term “prevention,” which I distinguish as “phenotypic prevention” and “genotypic prevention.” Phenotypic prevention describes medical efforts to forestall the clinical manifestation of a genetic disease in an at-risk patient, like newborn screening and dietary prophylaxis for phenylketonuria. Genotypic prevention, by contrast, describes efforts to avoid the transmission of particular genotypes to the next generation, like selective termination following intrauterine diagnosis. Genotypic prevention is either performed on behalf of a prospective parent (or two) as a reproductive risk reduction strategy, or as a public health intervention to reduce the incidence of a disease in the larger population. Conflating phenotypic and genotypic prevention in discussions of germ-line gene therapy is dangerous, because it blurs the line (well-established in clinical genetics) between medical interventions appropriate to prescribe to individuals and families, and reproductive choices that should be theirs alone to make. As the new genetic medicine emerges, its pioneers should be careful to articulate their professional goals in ways that respect that important moral boundary, by explicitly excluding genotypic prevention from among them. This paper criticizes the argument that germ-line gene therapy is rendered superfluous by the availability of preimplantation and prenatal screening techniques. Gene therapy and genetic screening actually address two quite different preventive goals: the former attempts to prevent the manifestation of a disease phenotype within a patient, and the latter attempts to prevent the occurrence of a case of illness within a family, by avoiding the birth of individuals with particular genotypes. While case reduction is a legitimate goal for individuals and families to pursue, I argue that gene therapists should follow the lead of their colleagues in clinical genetics, and eschew it as an overarching aim of their work. This perspective both bolsters the case for developing human germ-line gene therapy techniques, and places new constraints on its clinical use.