Risks of gene therapy should be weighed against lack of alternatives for many diseases

Editor—Kimmelman provided a comprehensive discussion about the risks and ethics of gene therapy.¹ We certainly cannot predict the future, but the risks should be weighed against the complete lack of alternative options for many of the diseases discussed.

Figure 1.

Artwork of gene therapy

Credit: ©JIM DOWDALLS/SPL

The two cases of T cell leukaemia in the X linked severe combined immunodeficiency gene therapy trial are presented as typical examples of malignant transformation. However, that treatment entailed the modification of immature stem cells, which may present additional risks.² Much work is being done in vector design to lessen these risks. Relative risks and toxicities are also likely to be linked to the disease type and target cell. For non-lethal disorders such as the inherited retinal dystrophies, minimising risk is of even more importance. However, gene transfer to a post-mitotic cell such as a photoreceptor by using a vector with limited genomic integration, such as recombinant adeno-associated virus, is much less likely to be mutagenic.

The risks of gene therapy must be weighed carefully against the risks and efficacy of existing treatment. Conventional treatments such as organ transplantation, which are no longer considered experimental, are associated with substantial morbidity and mortality.³ The difficult balance is to steer a path between the ethical application of new untested strategies with the potential to improve health care, and a position of caution. As with conventional medicines, the risks and ethics of gene therapy should probably be reflected in this light.