Gain of Function
In October 2014, the White House Office of Science and Technology Policy (OSTP) announced a funding pause on selected “Gain of Function” (GoF) research involving influenza viruses, SARS coronavirus, and MERS coronavirus, namely experiments that are “reasonably anticipated to confer attributes to influenza, MERS, or SARS viruses such that the virus would have enhanced pathogenicity and/or transmissibility in mammals via the respiratory route” (White House OSTP Moratorium Memo). OSTP called for a deliberative process to evaluate the risks and potential benefits of this research, which will culminate in the development and adoption of a new US Government (USG) policy governing the funding and conduct of GoF research and the release of the funding pause.
The National Science Advisory Board for Biosecurity (NSABB) is serving as the official federal advisory body on GoF research issues and is responsible for developing recommendations for the appropriate level of Federal oversight of GoF research. To inform the NSABB’s deliberations on this issue, Gryphon Scientific was contracted by the NIH Office of Science Policy to conduct risk and benefit assessments (RBA) of GoF research involving the pathogens subject to the funding pause. Our assessment was divided into four components: (1) biosafety risk assessment, (2) assessment of biosecurity risks due to intentional acts against the laboratory, (3) assessment of biosecurity risks due to misuse of information, and (4) benefit assessment. Contained on this page are Gryphon’s final and draft reports to NIH OSP and NSABB, Gryphon’s presentations on the RBA, as well as Supplemental Information supporting the conclusions and findings in the report.
For further information on the federal moratorium on GoF research and the framework that guided Gryphon’s RBA, see:
White House OSTP Moratorium Memo
NSABB Framework for Guiding the Risk Benefit Analysis

Gain of Function Report

Presentations

Risk and Benefit Analysis (RBA) of Gain of Function Research 050515

Risk and Benefit Analysis (RBA) of Gain of Function Research 092815

Risk and Benefit Analysis (RBA) of Gain of Function Research 010716

Gaps and Future Considerations of Gain of Function RBA 02102016

Publications

Kavita M. Berger. What Scientists Should Know About Security Threats. 9 Dec 2016. 354(6317): 1237-1239.
AbstractReprintFull Text

 

Supplemental Information

Risk Assessment – Supplemental

Detailed Parameters of Quantitative Models

RA_Detailed Parameters of the Laboratory Incident Event Tree Model

RA_Dose Response – This report explains how exposure data, as computed from the event tree model, was used to compute the probability an exposure following a loss-of-containment event leads to a primary infection of a laboratory worker.

RA_Detailed Parameters and Methodology of the Fomite Model

RA_Data on Viral Stability and Transfer – This report reviews available scientific literature on the transfer efficiency and environmental stability of SARS- and MERS-CoV, and influenza viruses, and was used to inform parameters in the fomite model.

RA_Detailed Parameters of the Branching Process Model

RA_Detailed Parameters of the BARDA Interactive Flu Model

RA_Demographic Data Supporting BARDA Interactive Flu Modeling – This report reviews available global demographic data that were used to inform parameters in each region modeled in the BARDA Interactive Flu Model.

Event Trees

This section contains graphical representations of each of the laboratory incident event trees.

RA_Event Tree – Animal Bite

RA_Event Tree – Animal Escape

RA_Event Tree – Animal Respiration

RA_Event Tree – Centrifuge Top Half

RA_Event Tree – Shipment

RA_Event Tree – Slip During Necropsy

RA_Event Tree – Solid Waste

RA_Event Tree – Spill and Centrifuge Subtree

RA_Event Tree – Spill Top Half

RA_Event Tree – Splash

RA_Event Tree – Worker Response

Human Epidemiological and Sociological Data

RA_R0 of CoV – This report reviews available data on the R0 of SARS- and MERS-CoV, and was used to inform parameter ranges sampled in the quantitative risk models.

RA_CoV Disease Course – This report reviews epidemiological parameters of infection with SARS-CoV and MERS-CoV, and these data were used to inform parameter ranges sampled in the quantitative risk models for the coronaviruses.

RA_Influenza Disease Course – This report reviews epidemiological parameters of infection with influenza, and these data were used to inform parameter ranges sampled in the quantitative risk models for influenza.

RA_Antiviral and Vaccine Efficacy – This report reviews available scientific data on the efficacy of antivirals and vaccines against influenza, and these data were used to inform parameter ranges sampled in the quantitative risk models for influenza.

Laboratory PPE, Experiment, and Animal-Related Supporting Information

RA_Avian Influenza Titers in Mammals – This report reviews available scientific data on the avian influenza titers in infected laboratory mammals, and these data were used to inform parameter ranges sampled in the laboratory incident models.

RA_CoV Titers in Saliva – This report reviews the titer of coronaviruses found in laboratory animal saliva, and these data were used to inform parameter ranges sampled in the laboratory incident models.

RA_Culture Flask Durability – This report reviews primary data collected by Gryphon Scientific as to the probability that a tissue culture flask breaks after being dropped, and these data were used to estimate the volume of a laboratory spill incident.

RA_Protection afforded by PAPRs – This report reviews available data on the protection factors and failures rates of PAPRs, and these data were used to inform parameter ranges sampled in the laboratory incident models.

Avian Influenza-Related Supporting Information

RA_Selected and Notable Avian Influenza Outbreaks – This report reviews several notable historic avian influenza outbreaks, to demonstrate the significant variability between strains and outbreaks, which prevented detailed quantitative modeling of the consequences of a loss-of-containment event involving avian influenza.

RA_Duck Populations – This report reviews duck populations near two of the gain-of-function laboratories visited. Data were used to inform the probability of an avian influenza outbreak following a liquid waste loss of containment event.

RA_Minute Tidal Volume of Ducks – This report reviews available scientific literature on the breathing volume of ducks; these data were used to inform the risk of a human infection by an infected duck via respiratory aerosols.

Other Risk-Related Supplemental Material

RA_Calculating Earthquake Risk – This report reviews available seismic and geological data used to compute the probability of, and damaged caused by, an earthquake at a gain-of-function laboratory.

RA_Protection by 2009 H1N1 Against Infection with 1918 H1N1 – This report reviews the available literature on the protection afforded by either vaccination against or infection by the 2009 H1N1 pandemic influenza strain against infection with the 1918 H1N1 pandemic influenza strain. These data were used to estimate the fraction of the population that is currently immune to infection with the 1918 strain.

RA_UV Inactivation of Influenza and CoV – This report reviews the available scientific data on the rate at which viruses are inactivated by sunlight during daylight hours. These data were used to inform parameters sampled in the environmental release plume models that demonstrated no plausible aerosol release scenario of consequence.

Benefit Assessment – Supplemental

This section of the supplemental material contains several short reports with data and detailed analyses that further support the conclusions presented in Chapters 9 and 15 of Gryphon Scientific’s Risk and Benefit Assessment on Gain of Function Research involving influenza viruses and coronaviruses.

BA_Landscape of GoF and alt-GoF Research – This report details the generalized set of gain-of-function (GoF) experiments that capture the range of GoF studies conducted in the scientific literature to date and the generalized set of alt-GoF experiments that could provide the same or similar information. (See Section 9.2.3 for a description of how these generalized experiments were defined.) Generalized experiments are broken down by GoF phenotype, and specific examples of each experiment type are provided.

BA_State of Surveillance – This report focuses on the state of influenza and coronavirus surveillance. Gaps in surveillance and the implications of those gaps for the utility of surveillance-based alt-GoF approaches are highlighted. These findings have implications for the feasibility and utility of alt-GoF approaches that rely on surveillance data and for GoF benefits to surveillance.

BA_Animal Models – This report reviews the state of animal models for influenza viruses and coronaviruses, summarizing the benefits and limitations of each model system and the types of experiments for which each animal model is suitable. These findings have implications for the feasibility and utility of both GoF and alt-GoF experimental approaches.

Other Supplemental Information

Interview Guides

Additional Interview Data – Research Proliferation, Practical Considerations for GoF Policies, and Limitations of Alternative Approaches – This document summarizes interview data that were not directly incorporated into the RBA but are relevant to the overall deliberative process for developing a new USG GoF research policy and may inform the NSABB’s deliberations.

Case Studies