The ethics of gene therapy: balancing the risks.

Gene therapy research is characterized by heightened uncertainty about the risks associated with the complex products involved, particularly the risk of genotoxicity. Recognizing that uncertainty concerning risks is inescapable in first-in-human clinical trials of gene therapy, decisions on how to balance the risks nevertheless must be made. Ethics can facilitate translational progress by, first, evaluating decision-making processes during risk assessment; and second, focusing on questions that require a degree of subjective judgement. Such assessments include determining the level of risk that is acceptable in trials, the category of patients that should be exposed to the risks, and the level of certainty with respect to risk that is required for both researchers and participants to make decisions. Analysis of these issues is affected by the burden of illness, existing treatment alternatives and the possible benefits of gene therapy. Patients' attitudes and experiences in this regard can reasonably inform the decision-making of researchers. Reflecting upon the approaches used to balance risks and possible benefits in gene therapy trials may improve decision-making processes across the spectrum of decisions that are made from the initial conception of a study up to decisions by research participants about consent. This manner of reflection facilitates the advancement of science, while protecting the welfare of research participants.