Gain-of-Function Influenza Research: A New Paradigm or an Engineered Pandemic? A Comprehensive Assessment of the Merits and Risks of Gain-of-Function Experiments and a Proposed Framework Going Forward

• Main Author: Banerjee, Debolina
• Other Authors: Shenk, Thomas
• Format: Bachelor Thesis
• Language: English
• Published: 2014
• Subjects: Avian flu
• Online Access: http://arks.princeton.edu/ark:/88435/dsp01b8515n57k

Influenza A virus poses a grave threat to individual and public health, as seasonal influenza kills upwards of 500,000 people globally every year. Gaping holes in our knowledge of the complex mechanisms underlying its rapid evolution and cross-species transmission persist despite concerted research efforts to elucidate these processes. In light of an imminent pandemic capable of exterminating tens of millions of people and animals in a short period of time, the dire need for intensive basic biology research is indisputable. In 2011, two NIH- supported research groups conducted gain-of-function experiments to study the factors involved in the virulence and transmissibility of the highly pathogenic H5N1 avian influenza virus in ferrets, the best available mammalian model organism to study influenza infection in humans. By introducing mutations into the viral genome and serially passaging these flu strains through ferret animals, the Fouchier research group and the Kawaoka research group were able to identify specific mutations that rendered these lab-modified H5N1 variants transmissible in ferrets. After a public announcement of inducing a highly pathogenic avian flu virus H5N1 to become transmissible in mammals by Ron Fouchier, the principal investigator of one of the research groups that conducted these gain-of-function studies, the National Science Advisory Board for Biosecurity (NSABB) reviewed the details of the studies conducted. After instituting a voluntary research moratorium on gain-of-function influenza research, the NSABB, in an unprecedented move, recommended that both papers be published in redacted form, citing a threat to national security. This seminal event stirred a polarized debate centered on issues of academic freedom, censorship, and biosecurity that still persists today. These gain-of- function experiments are classified as ¿dual-use research of concern¿ (DURC), or research that can be used both for good and ill. Open access publication of complete manuscripts posed a biosecurity risk, as ...