Gain-Of-Function Research

Risks

Biosafety and biosecurity concerns, potential for laboratory accidents, dual-use research (can be used for beneficial or malevolent purposes), creation of dangerous pathogens.

Purpose

Understanding disease mechanisms, developing effective therapies, innovation in agriculture, sustainability, and medicine, transforming cells and viruses into new biotechnologies.

Oversight

Existing research oversight, careful review prior to, during, and after funding, strict protocols for 'Gain of Function Research of Concern'.

Definition

Experiments that genetically alter an organism to give it new or enhanced functions, often increasing the capability of a pathogen to cause disease (e.g., transmissibility or virulence), for the purpose of understanding mechanisms and developing effective therapies.

Scientific Fields

Virology, Microbiology, Molecular Biology, Synthetic Biology

Criticism by Rand Paul

Allegedly U.S.-funded and outsourced to China, part of a 'COVID Cover Up' orchestrated by Dr. Anthony Fauci, eroded public trust and fueled vaccine hesitancy.

Gain-of-function research broadly refers to experiments that genetically alter an organism to give it new functions that can be used in agriculture, sustainability, and medicine. In a few cases, gain-of-function research increases the capability of an organism to cause disease with the purpose of understanding these mechanisms and developing effective therapies. Existing research oversight ensures gain-of-function research is carefully reviewed prior to, during, and after funding. [...] ## Why It Matters Gain-of-function research is an important scientific tool that can lead to major breakthroughs in developing ways to fight diseases such as cancer or to innovate in areas such as energy and sustainability. Enabled by synthetic biology, gain-of-function research involves the application of engineering principles to biology by genetically modifying organisms to give them new or enhanced abilities. [...] Gain-of-function research can be broadly defined to include large portions of virology, microbiology, molecular biology, synthetic biology, and other areas that are vital to transforming cells and viruses into new biotechnologies, therapies, and tools. New legislation is not needed; instead existing oversight mechanisms and their continuous updates will ensure that potentially dangerous research is adequately safeguarded.

Gain of function is a broad term that can encompass almost any type of research aimed at understanding mechanisms and processes. Gain of function techniques are used in research to alter the function of an organism in such a way that it is able to do more than it used to do. (The inverse process in research is referred to as “loss of function.”) This may be accomplished in the lab by adding to or changing the organism’s genetic sequence, and this type of research has had a positive impact on [...] Outside of the lab, where microbes are facilitated by only natural selection in their respective environments, gain of function is a naturally occurring evolutionary process. In fact, microorganisms accumulate mutations in their genomes almost every time they divide. For example, antibiotic resistance is often acquired when bacteria gain and incorporate entire plasmids into their genomes. The process is further demonstrated by the continued emergence of SARS-CoV-2 variants. [...] Gain of Function Research Certain types of gain of function research -- for example, Gain of Function Research of Concern, Dual Use Research of Concern or Enhanced Potential Pandemic Pathogen (E3P) -- raise important biosafety and/or biosecurity concerns. While these are an extremely small subset of gain of function experiments (estimated at less than 1 percent), they require a higher level of review and are subject to strict protocols.

“Basically, gain-of-function research is based on techniques in the laboratory that change microbes – viruses and bacteria – to become either more transmissible or more virulent,” Sweat said. As he prepared the audience for the debate, Sweat also noted that gain-of-function research has been part of the discussion about the possible origins of the coronavirus pandemic. [...] In concluding his presentation, he said: “Gain-of-function research is only a small part of virology and microbiology research. So, we need to be careful about what we actually are discussing and deciding shouldn't happen. But I think the purported benefits of gain-of-function research are exaggerated and dependent upon subsequent downstream surveillance and therapeutics, which you're not guaranteed.” [...] He took a more serious tone as he described gain-of-function research from a critical perspective. “It’s intended to focus on experiments that may increase the transmissibility and/or the virulence of pathogens,” Flume said. “It's adaptation research. Scientists change things and look at the impact.” But he noted that the more he researched what gain of function really means, the blurrier things got.

Subbarao explained that routine virological methods involve experiments that aim to produce a gain of a desired function, such as higher yields for vaccine strains, but often also lead to loss of function, such as loss of the ability for a virus to replicate well, as a consequence. In other words, any selection process involving an alteration of genotypes and their resulting phenotypes is considered a type of Gain-of-Function (GoF) research, even if the U.S. policy is intended to apply to only [...] During Session 3 of the symposium, Dr. Yoshihiro Kawaoka, from the University of Wisconsin-Madison, classified types of GoF research depending on the outcome of the experiments. The first category, which he called “gain of function research of concern,” includes the generation of viruses with properties that do not exist in nature. The now famous example he gave is the production of H5N1 influenza A viruses that are airborne-transmissible among ferrets, compared to the non-airborne