Gain-of-function research

Gain-of-function research (GoF research or GoFR) is medical research that genetically alters an organism in a way that may enhance the biological functions of gene products. This may include an altered pathogenesis, transmissibility, or host range, i.e., the types of hosts that a microorganism can infect. This research is intended to reveal targets to better predict emerging infectious diseases and to develop vaccines and therapeutics. For example, influenza B can infect only humans and harbor seals.^[1] Introducing a mutation that would allow influenza B to infect rabbits in a controlled laboratory situation would be considered a gain-of-function experiment, as the virus did not previously have that function.^[2][3] That type of experiment could then help reveal which parts of the virus's genome correspond to the species that it can infect, enabling the creation of antiviral medicines which block this function.^[3]

In virology, gain-of-function research is usually employed with the intention of better understanding current and future pandemics.^[4] In vaccine development, gain-of-function research is conducted in the hope of gaining a head start on a virus and being able to develop a vaccine or therapeutic before it emerges.^[4] The term "gain of function" is sometimes applied more narrowly to refer to "research which could enable a pandemic-potential pathogen to replicate more quickly or cause more harm in humans or other closely-related mammals."^[5][6]

Some forms of gain-of-function research (specifically work which involves certain select agent pathogens) carry inherent biosafety and biosecurity risks, and are thus also referred to as dual use research of concern (DURC).^[7] To mitigate these risks while allowing the benefits of such research, various governments have mandated that DURC experiments be regulated under additional oversight by institutions (so-called institutional "DURC" committees)^[8] and government agencies (such as the NIH's recombinant DNA advisory committee).^[9][10][11] A mirrored approach can be seen in the European Union's Dual Use Coordination Group (DUCG).^[12][13][14]

Importantly, regulations in the United States and European Union both mandate that at least one unaffiliated member of the public should be "active participants" in the oversight process.^{[15][16][17][18]} Significant debate has taken place in the scientific community on how to assess the risks and benefit of gain-of-function research, how to publish such research responsibly, and how to engage the public in an open and honest review.^{[19][20][7][21]} In January 2020, the National Science Advisory Board for Biosecurity convened an expert panel to revisit the rules for gain-of-function research and provide more clarity in how such experiments are approved, and when they should be disclosed to the public.^[22][23]