The Octopus of Reference Standards

When gene transfer researchers perform an experiment, how do they measure the dose of their vectors?  For that matter, when investigators perform a study using any novel biologic, how have they characterized their agents?

Few would think the questions are ethically significant. But consider the fact that research teams often use different techniques to determine vector dosage, and as a consequence, results from different human and animal studies cannot be compared with each other.

In the July issue of Molecular Therapy, Richard Snyder and Philippe Moullier outline international efforts to estabish reference standards for AAV vectors (a class of viral vectors widely used in gene transfer studies). After about six years (and nearly twice that of trials using human beings), reference standards for two serotypes (AAV2 and AAV8) will soon be available. The authors describe a number of logistic and funding problems for establishing reference standards. Not mentioned are the numerous sociological challenges with herding feline-like researchers.

In my book, I argue that standards represent a critical vehicle for risk management in novel research arenas: small-scale human safety studies have limited value unless results can be linked up with other human studies to identify trends. Standard setting, and the octopus–like extension of standards into all preclinical and clinical studies–thus have important ethical implications. IRBs reviewing early phase novel agent protocols should be on the alert where study agents are not characterized using reference standards (photo credit: Roadsidepictures, 2007)