Princeton University Library Catalog

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

Banerjee, Debolina [Browse]
Senior thesis
Shenk, Thomas [Browse]
Princeton University. Department of Molecular Biology [Browse]
Class year:
128 pages
Summary note:
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 knowledge of these studies could be used by malicious individuals to potentially create a pandemic strain of influenza that could be used as a biological weapon against other nations. Scientists, policymakers, national security experts, and concerned members of the public alike question whether the merits of this research outweighed the accompanying risks and whether this type of research should be undertaken in the first place. This prompted further questions regarding the regulation of DURC, leading to a reform in NIH Guidelines and persisting questions about the future of gain-of-function experiments. After investigating the history of DURC in the United States and evaluating lessons learnt from the historical precedent of recombinant DNA technology and the Asimolar Conference in the 1970s, I conducted a comprehensive cost-benefit assessment and concluded that the merits of gain-of-function influenza research outweigh the potential risks. My investigation culminated in the formulation of a framework for evaluating the most salient issues concerning the future of gain-of-function influenza research. Thorough evaluation of these salient issues informed the proposals for policy reform presented in the final chapter, which address the need for legally binding biosecurity and biosafety measures in the regulation of DURC research in order to mitigate the threat to national security and public health.