Gene Therapy Oversight: Lessons for Nanobiotechnology

Abstract

Oversight of emerging technology such as nanobiotechnology raises complex issues at the intersection of institutional design, regulatory theory, and science. Too little of the literature offering recommendations for oversight takes advantage of the rich history of U.S. oversight design efforts in order to harvest the lessons for prospective design. This article systematically analyzes the history of oversight for human gene transfer research (“gene therapy”) to learn the lessons for design of nanobiotechnology oversight. The human gene therapy oversight experience presents an important model of oversight for science and technology in the research phase with substantial attendant uncertainties. Much of nanobiotechnology that has application to human health is in research trials or will be in the foreseeable future. The uncertainties about the behavior and toxicity of many materials engineered at the nanoscale (usually defined as 1-100 nanometers) are great, especially more complex and interactive materials (often called “active” as opposed to “passive” nanomaterials). In addition to these similarities between the oversight challenges posed by gene therapy and nanobiotechnology, gene therapy oversight is already beginning to address nanobio directly, through review of protocols using non-viral nano-vectors to deliver DNA or RNA within the human body.

The design of gene therapy oversight, which grew out of oversight for recombinant DNA (rDNA) research in the mid-1980s, exemplifies complex review that combines federal with local institutional oversight and cuts across more than one federal agency. Gene therapy oversight adds centralized federal review at the National Institutes of Health's Office of Biotechnology Activities (OBA) and its Recombinant DNA Advisory Committee (the RAC) plus federal review at the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER) to standard oversight of human subjects research at the researcher's institution by the Institutional Review Board (IRB) and, for some research, the Institutional Biosafety Committee (IBC). This article traces the evolution, successes, and failures of this complex oversight system. The article evaluates the oversight system based on the literature, public opinion data, and a preliminary elicitation of expert views using a survey instrument designed to evaluate oversight systems.

The analysis yields a range lessons for oversight of nanobiotechnology. It sheds light on the relative merits of using preexisting oversight frameworks versus innovating, oversight options to address real but uncertain risks, oversight approaches to deal flexibly with evolving science, trade-offs in assuring public access to information, and challenges in coordinating oversight conducted by more than one federal agency. The article demonstrates the value of rooting oversight design for emerging technology in historical assessment of cognate oversight experiences.

Keywords: oversight, emerging technology, nano, nanotechnology, nanobiotechnology, human gene transfer research, gene therapy