Recent developments in gene transfer: risk and ethics

doi:10.1136/bmj.330.7482.79

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Jonathan Kimmelman, research associate (jonathan.kimmelman@mcgill.ca)1

¹ Clinical Trials Research Group, Biomedical Ethics Unit, Faculty of Medicine, McGill University, 3647 Peel Street, Montreal, QC, Canada H3A 1X1

Accepted 9 November 2004

Introduction

Since the early 1990s, investigators have toiled to establish the transfer of genes to human somatic cells as a valid therapy (fig 1). The potential of gene transfer was highlighted by three trials, involving participants with haemophilia B and two types of severe combined immunodeficiency—X linked and adenosine deaminase deficient.1^–3 Yet even the most successful trials of gene transfer have engendered questions about its prospects. In the haemophilia B trial the detection of vector—the agent which carries genes to cells (fig 2)—in participants' semen raised concerns about modifications of the germline.4 The results of the X linked severe combined immunodeficiency trial were offset by unexpected, vector induced leukaemia in two participants.5

Fig 1

Number of gene transfer trials approved worldwide has increased since 1989; 77% have been conducted in the United States and the United Kingdom. Most trials have used virus based vectors (70%), are phase 1 (63%), and involve investigational treatments for cancer (66%). Adapted from Wiley Gene Therapy Clinical Trial Database (http://www.wiley.co.uk/wileychi/genmed/clinical/)

Fig 2

In a gene transfer, therapeutic DNA is combined with a vector (often of viral origin). Vectors can be injected into recipient's tissue directly or used to modify cells ex vivo for transplantation to the recipient

Several hazards associated with gene transfer have been verified by clinical experience and others are predicted on theoretical grounds. It therefore may be worth considering whether risks shown in studies of human gene transfer present any unusual ethical and social challenges and, if so, what should be done to tackle them. In this article I review several matters relating to human gene transfer—safety features that distinguish traditional drugs from agents used to transfer genes, ethical issues raised by uncertainties about risk and toxicological properties, and studies on safety.