Potential Risks and Benefits of Gain-of-Function Research: Summary of a Workshop.

https://www.ncbi.nlm.nih.gov/books/NBK285579/

The field of virology, and to some extent the broader field of microbiology, widely relies on studies that involve gain or loss of function. In order to understand the role of such studies in virology, Dr. Kanta Subbarao from the Laboratory of Infectious Disease at the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH) gave an overview of the current scientific and technical approaches to the research on pandemic strains of influenza and Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) coronaviruses (CoV). As discussed in greater detail later in this chapter, many participants argued that the word choice of “gain-of-function” to describe the limited type of experiments covered by the U.S. deliberative process, particularly when coupled with a pause on even a smaller number of research projects, had generated concern that the policy would affect much broader areas of virology research

ALTERNATIVES TO GOF RESEARCH

The essence of the debate around the risks and benefits of GoF research and the concerns it raises have naturally encouraged virologists on both sides of the debate to consider alternative methodological approaches. During his talk, Kawaoka discussed alternatives to GoF research mostly applicable to influenza research, such as loss-of-function research, use of low pathogenicity viruses, and phenotypic analyses. He further cited a review paper in which Lipsitch and Galvani (2014) stated that “alternative scientific approaches are not only less risky, but also more likely to generate results that can be readily translated into public health benefits.” However, Kawaoka argued through specific examples that alternatives do not always provide the full answer to key questions. For instance, he cited work by Tumpey et al. (2007) and Imai et al. (2012) on mutations responsible for the loss of transmission capabilities of the 1918 influenza strain between ferrets and noted that this work required GoF research because a loss-of-function approach did not provide the complete picture. In addition, although working with low pathogenic avian influenza viruses provides a safer approach, Kawaoka explained that “highly pathogenic avian influenza differ from low pathogenic viruses in their kinetics of virus replication and tropism” and therefore the data can be misleading. Other alternatives discussed by Kawaoka and Dr. Robert Lamb, Northwestern University, in Session 8 of the symposium were cited from the recent review paper by Lipsitch and Galvani (Box 3.3). Kawaoka concluded that even if these approaches offer safer alternatives to GoF research of concern, for some questions researchers cannot rely solely on them because the phenotype of and the molecular basis for these new traits have been identified by GoF research but not by alternative approaches.